Double-blind, Placebo-controlled Antibiotic Treatment Study of Small Intestinal Bacterial Overgrowth in Children With Chronic Abdominal Pain

Abstract

Background and Objectives: Chronic abdominal pain (CAP) in children may be a precursor to irritable bowel syndrome (IBS) in adults. The prevalence of abnormal lactulose breath tests (LBT) suggesting small intestinal bacterial overgrowth (SIBO) has been reported as 91% in children with CAP and 35% in healthy controls. In addition, patients with IBS with SIBO who responded to nonabsorbable antibiotic treatment with normalization of LBT reported 75% global improvement in symptoms. The aim of the study was to test whether treatment with a nonabsorbable antibiotic may reduce symptoms in children with CAP.

Methods: Seventy-five children ages 8 to 18 years with CAP based on Rome II criteria were enrolled. Subjects underwent baseline LBT and completed symptom-based questionnaires. They were then randomized in a 2:1, double-blind fashion to receive a 10-day course of 550 mg of rifaximin or placebo 3 times per day (t. i.d.). LBT and questionnaires were repeated 2 weeks after treatment.

Results: Forty-nine children received rifaximin and 26 received placebo. There were no differences in demographics between groups. Ninety-four percent who received rifaximin and 92% who received placebo had abnormal baseline LBT, suggesting SIBO (not significant [NS]). There was no significant difference in symptom improvement between groups; however, only 20% of children treated with rifaximin achieved a normalized repeat LBT, demonstrating successful treatment of SIBO.

Conclusions: Similar to adults with IBS, the prevalence of abnormal LBT suggesting SIBO in children with CAP is high; however, treatment with 10 days of rifaximin has low efficacy in normalizing LBT in this group. Additional studies are needed to determine whether a treatment approach with higher efficacy would lead to improvement in children with CAP.

Author Information

* Division of Gastroenterology and Nutrition, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, USA

† Gastroenterology Section, New Mexico VA Health Care System and the University of New Mexico, Albuquerque.

Received 23 April, 2010

Accepted 1 July, 2010

Address correspondence and reprint requests to Brynie Slome Collins, MD, Division of Gastroenterology and Nutrition, Children's Hospital Los Angeles, MS #78, 4650 Sunset Blvd, Los Angeles, CA 90027 (e-mail: bcollins@chla. usc. edu).

The present study was supported by the Saban Research Institute Research Career Development Fellowship Award, Clinical Research Academic Career Development Award, and the CHLA General Clinical Research Center (GCRC) through NIH NCRR GCRC Grant MO1 RR-46. It was also supported, in part, by an unrestricted grant from Salix Pharmaceuticals. Salix played no role in the conception of the hypothesis, experimental design, conduct of the study, data analysis, or preparation of the manuscript.

Dr Lin has IP rights in a related area. Dr Lin is supported by the NIH, the VA, and the Department of Defense.

ClinicalTrials. gov Identifier: NCT00619970.

The authors report no conflicts of interest.

Chronic abdominal pain (CAP) is a frequent and often debilitating childhood complaint. The overwhelming majority of children with CAP have a functional gastrointestinal disorder with symptoms not explained by anatomical or biochemical abnormalities. Although the exact prevalence of CAP is unknown, this diagnosis is responsible for 2% to 4% of all of the pediatric office visits in the United States, (1). with 13% to 19% of American school-age children experiencing weekly abdominal pain (2). Moreover, the abdominal pain and associated symptoms experienced by these children are often so severe that school performance, psychosocial function, and overall quality of life are impaired (3–5) .

Although a unifying pathogenesis has yet to be identified for CAP, several mechanisms have been proposed to explain the symptoms of this condition, including altered intestinal motility (6). abnormal visceral perception (7). and psychological factors (8). Recently, evidence has also pointed to an underlying gut microbial mechanism for CAP (9,10) .

Normally, in humans, the concentration of gut microbes is greatest in the colon, dropping steeply from 10 10–12 organisms/mL in the cecum to 10 5–8 organisms/mL in the proximal ileum and 10 0–4 in the jejunum and duodenum (10). Hydrogen produced by bacterial fermentation is eliminated, in part, by methanogens or sulfate-reducing bacteria that convert hydrogen to methane or hydrogen sulfide (11,12). These microorganisms are competitive because the stool of an individual usually produces high concentrations of either methane or hydrogen sulfide.

When the microbial population native to the large intestine migrates proximally into the small intestine, a shift in the host–gut microbial relationship occurs known as small intestinal bacterial overgrowth (SIBO) (13). In patients with SIBO, abnormal microbial fermentation can occur in the small intestine and may be detected by measuring hydrogen and methane in the exhaled breath after ingestion of a fermentable substrate such as lactulose. This response is the basis for the lactulose breath test (LBT) (14). Because methanogens reside in the large intestine, with their concentration highest in the left colon (15). methane is normally absent from the exhaled breath during a 180-minute LBT.

Similar to patients with CAP, patients with SIBO complain of postprandial bloating, abdominal pain, nausea, vomiting and diarrhea, and constipation, as well as a variety of extraintestinal symptoms such as fatigue. In our recently published study (9). abnormal microbial fermentation suggesting SIBO was found in 91% of patients with CAP compared with 35% in healthy controls. These data are similar to that of Scarpellini et al (16). who found that 65% of children with irritable bowel syndrome (IBS) had SIBO. Abnormal microbial fermentation has also been reported in 78% to 84% of adult patients with IBS compared with 20% in healthy controls (17,18). In addition, in a randomized, double-blind, placebo-controlled trial, patients with IBS who responded to treatment with a nonabsorbable antibiotic, as shown by normalization of the LBT, reported 75% global improvement in symptoms (18). To date, there are no published data on the effect of antibiotic treatment in children with CAP. Therefore, the aim of the present study was to test the hypothesis that treatment of SIBO with a nonabsorbable antibiotic may reduce symptoms in children with CAP.

Double-blind-randomized, Placebo Controlled Trial for Chemotherapy-associated Oral Mucositis Using Doxycycline Hyclate

Information source: Metropolitan Autonomous University

ClinicalTrials. gov processed this data on August 23, 2015

Status: Not yet recruiting

Sponsored by: Metropolitan Autonomous University

Official(s) and/or principal investigator(s):

Sergio Ponce de Leon, MD, Study Director, Affiliation: Instituto Nacional de Ciencias MГ©dicas y NutriciГіn

Overall contact:

Velia Ramirez-Amador, PhD, Phone: 5255 5483 7206, Email: veliaram1@gmail. com

Summary

Background. Mucositis is a complication of chemotherapy with no effective treatment. Aim. To evaluate the efficacy of sub-microbial doses of doxycycline hyclate in preventing the development of oral mucositis in patients with acute leukemia (AL) treated with induction chemotherapy. Hypothesis. Doxycycline hyclate administration in sub-microbial dosage will reduce the incidence of oral mucositis in patients with AL who receive induction chemotherapy. Methods. Double-blind, randomized, placebo-controlled clinical trial. At the Cancer National Institute (INCan), adult patients (> 18 years of age) with acute leukemia of recent diagnosis, scheduled to receive induction chemotherapy will be enrolled in the study. Written informed consent from the patients will be obtained preceding inclusion in the study. At baseline and 3-times per week, during 21-days, patients will have an oral examination performed using the Oral Mucositis Assessment Scale (OMAS), oral pain, difficulty to swallow, and salivary flow measurements will be recorded. A sample size of 164 subjects has been calculated, 74 subjects in each arm of the study. The primary end point of this study to evaluate the efficacy will be the proportion of patients treated with doxycycline or placebo without oral lesions associated with OM, during the 21 days of follow-up. Efficacy will be evaluated if the proportion of complete response (CR) is significantly higher than the proportion of events in the placebo group. Additional secondary endpoints will be the partial resolution of the oral lesions, the incidence of infections and the mortality in the study groups during the 21 days of follow-up. Results will be analyzed by using Chi-squared test and Wilcoxon-Mann-Whitney rank sum test.

Clinical Details

Official title: Phase 2 Double-blind, Randomized, Placebo Controlled Clinical Trial for the Prevention of Oral Mucositis Using Sub-microbial Doses of Doxycycline Hyclate in Patients With Acute Leukemia Receiving Induction Chemotherapy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Primary outcome: Complete response

Secondary outcome: Partial resolution of oral lesions, incidence of infections and mortality.

Detailed description: Background. Mucositis is a complication of chemotherapy with no effective treatment. Aim. To evaluate the efficacy of sub-microbial doses of doxycycline hyclate in preventing the development of oral mucositis in patients with acute leukemia (AL) treated with induction chemotherapy. Hypothesis. Doxycycline hyclate administration in sub-microbial dosage will reduce the incidence of oral mucositis in patients with AL who receive induction chemotherapy. Methods. Double-blind, randomized, placebo-controlled clinical trial. At the Cancer National Institute (INCan), adult patients (> 18 years of age) with acute leukemia of recent diagnosis, scheduled to receive induction chemotherapy will be enrolled in the study. Written informed consent from the patients will be obtained preceding inclusion in the study. Stratification according to the type of acute leukemia (myeloblastic and lymphoblastic) will be done. Random number tables will be used with balance for every four subjects; coded boxes will be utilized to preserve double blinding. Patients will be randomly assigned to receive either a sub-microbial dose of doxycycline hyclate or placebo (50 mg per day), immediately before the initiation of induction chemotherapy and daily during the following 21 days after chemotherapy. At baseline and 3-times per week, during 21-days, patients will have an oral examination performed using the Oral Mucositis Assessment Scale (OMAS). Also oral pain and difficulty to swallow will be recorded using a visual analogue scale. Also in each visit, salivary flow measurements (Schirmer's test modified version) will be done. The OMAS system is a validated index that evaluates the severity of oral mucositis by measuring the degree of ulceration/pseudomembrane and erythema in nine sites of the oral mucosa (upper and lower lip, right and left inner cheek, right and left ventral and lateral tongue, floor of the mouth, soft palate/fauces and hard palate). At each site, erythema is evaluated using a 3-point scale (0=none, 1=mild/moderate, 2=severe), and ulceration/pseudomembrane formation is evaluated using a 4-point scale (0=none, 1=cumulative surface area 3 cm2). The value of OMAS will be obtained by summing the erythema and ulceration/pseudomembrane sub-scores at each site and then averaging these scores across the affected sites. In order to rule out oral candidosis (OC), definitive diagnosis of OC requires the identification of pseudohyphae in exfoliative cytology samples stained with periodic acid Schiff. Likewise, the clinical diagnosis of herpes simplex virus (HSV) induced oral lesions will be confirmed by the virus-infected cells demonstrated in cytologic smears stained with Papanicolaou, and/or a clinical response to systemic antiviral therapy with acyclovir. A sample size of 164 subjects has been calculated, 74 subjects in each arm of the study. This estimate is based in the incidence of OM that is higher than 40% in patients with AL, and considering its reduction to half (20%), assuming an alpha value of 0. 05 (one-sided) and a minimum statistical power of 0. 80. The efficacy primary end point of this study will be the proportion of patients treated with doxycycline or placebo without oral lesions associated with OM, in the 21 days of follow-up. Efficacy will be evaluated if the proportion of complete response (CR) is significantly higher than the proportion of events in the placebo group. Additional secondary endpoints will be the partial resolution of the oral lesions, the incidence of infections and the mortality in the study groups during the 21 days of follow-up. Statistical analysis. Results will be analysed by using Chi-squared test and Wilcoxon-Mann-Whitney rank sum test.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria: Inclusion Criteria:

- Adult patients (> 18 years of age) with acute leukemia of recent

diagnosis, scheduled to receive induction chemotherapy.

- Capacity to give written informed consent.

- Ability to attend the follow-up visits.

- Inability to authorize a written informed consent.

Exclusion criteria

- Patients who start chemotherapy before 12 hours of the assigned treatment.

- Patients who have received less than 10 doses (5 days) of the assigned treatment.

- Requirement to receive ergot derivates.

- Patients who require the administration of acitretin/isotretinoin/tretinoin

- Patients that receive photosensitive drugs during the study period

(hydroxyquinone/retinoids or methoxsalen)

Locations and Contacts

Velia Ramirez-Amador, PhD, Phone: 5255 5483 7206, Email: veliaram1@gmail. com Instituto Nacional de Cancerologia, Mexico City 140180, Mexico; Not yet recruiting

Juan R Labardini-Mendez, MD, Phone: 56 28 04 00, Ext: 152, Email: labardini_juan@yahoo. com. mx

Juan R Labardini-Mendez, MD, Principal Investigator Additional Information

RamГ­rez-Amador V, Anaya-Saavedra G, Crespo-SolГ­s E, Camacho EI, GonzГЎlez-RamГ­rez I, Ponce-de-LeГіn S. Prospective evaluation of oral mucositis in acute leukemia patients receiving chemotherapy. Support Care Cancer. 2010 May;18(5):639-46. doi: 10.1007/s00520-009-0708-1. Epub 2009 Aug 6.

Starting date: May 2010

Last updated: March 15, 2010

Look for the gold standard: double-blind, placebo-controlled, randomized tests

The most reliable type of study — especially for clinical trials — is generally thought to be the randomized, placebo-controlled, double-blind study.

If you are looking at a clinical trial, a psychology study, or an animal study, and it hasn't been designed like this — and there isn't a good reason that it couldn't have been — then you might want to question the results.

Let's break down this terminology:

1) Randomized: This means that the participants in the study were randomly placed into the experimental group and the comparison group. This is important because if people get to choose, they might be more likely to pick one or the other because of some unexpected factor.

As a hypothetical example, maybe people who are more optimistic are more likely to want to try a new drug for anxiety rather than an old drug that's being used for comparison. And maybe optimism is linked to better outcomes for generalized anxiety disorder. The researchers could end up thinking that these people got better because of the drug when it was actually because they were innately going to do better anyway.

Similar problems can be introduced if researchers choose who goes into which category. That's why random is best.

2) Placebo-controlled: A controlled study has an appropriate comparison group, also called a control group. In medical studies, one comparison group usually gets a placebo — a fake intervention such as a sugar pill. This is in order to distinguish what the drug actually did from what a participant's psychological expectations did. (Placebo effects can be surprisingly strong — so strong that they can oftentimes relieve pain, among other health problems. And they've been getting stronger in recent decades, according to Steve Silberman's in-depth placebo story from Wired.)

A good placebo group should be as similar to the experimental group as possible. So, for example, if you were testing out a drug that's a large, red pill, you'd ideally want to give the people in your comparison placebo group a large, red pill that's the same in every way, but doesn't contain the drug. (Yes, even a pill's color and size can have a placebo effect.) Some studies go as far as to do sham surgeries. including anesthesia, incisions, stitches — the works.

3) Double-blind: A study is "blind" if the participants don't know whether they are in the experimental group or the control group. For example, you don't want someone knowing if she's received a real drug or a fake drug because her expectations could change the outcome of the study.

A study is "double-blind" if the researchers in personal contact with participants also don't know which treatment they are administering. You don't want the nurse giving out pills to know if they're real or not because then subtle differences in his behavior could influence patients — and therefore the results.

Card 6 of 9

Understand "significance"

Antifatigue Effects of Panax ginseng C. A. Meyer: A Randomised, Double-Blind, Placebo-Controlled Trial

Contributed equally to this work with: Hyeong-Geug Kim, Jung-Hyo Cho

Affiliation Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Jung-gu, Daejeon, South Korea

Contributed equally to this work with: Hyeong-Geug Kim, Jung-Hyo Cho

Affiliation Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Jung-gu, Daejeon, South Korea

Affiliation Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Jung-gu, Daejeon, South Korea

Affiliation Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Jung-gu, Daejeon, South Korea

Affiliation Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Jung-gu, Daejeon, South Korea

Affiliation Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Jung-gu, Daejeon, South Korea

Affiliation Department of Health Service Management Daejeon University, Dong-gu, Daejeon, South Korea

Affiliation Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Jung-gu, Daejeon, South Korea

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Control group

A control group refers to a group of patients in a study, that any intervention group is compared to. This helps to show that the intervention actually caused what was seen and that it wouldn’t have happened anyway.

One common type of control group is to use a placebo.

In the example above, all patients get the best treatment with or without the new drug.

If, for example, this is a new HIV drug and the best treatment already includes 3 active drugs, then it could be difficult to see any difference between the new drug and the placebo, because both groups will already do very well.

Another type of control group is a group where no intervention takes place.

This example might be used where there is something about the trial drug that makes using a placebo difficult – perhaps because it is given by injection.

The difficulty of not randomising the control group to having a placebo is that you can never be sure whether some of the things (both good and bad) that happened to patients in the active drug arm, are not due to chance.

More importantly, people in each arm may behave differently because they know they are getting active drug, for example, by reporting more side effects.

The example below uses a drug or combination that has already been studied as a control group.

This is still generally the type of trial design used for studying a new HIV drug in people who have not yet used HIV treatment. This is generally okay, so long as the new drug turns out to be better than, or at least as good as, the current standard of care.

For this reason, early trials with this design should not enrol people who have advanced HIV (for example with CD4 counts less than 100 cells/mm3) as these people will need to rely on a proven treatment.

Randomising patients should mean that important factors – both known and unknown – are likely to be distributed between each group. For example, having the similar numbers of women, Caucasians, smokers, CD4 counts etc in each group.

Last updated: 21 July 2009.

Intervention: Icatibant (Drug); Placebo (Drug)

Status: Recruiting

Sponsored by: Shire

Official(s) and/or principal investigator(s):

Vipin Aggarwal, MD, MPH, Study Director, Affiliation: Shire

Overall contact:

ShireHGT Call Center, Phone: +1-866-842-5335, Email: US_ShireHGT_Medicalinformation@shire. com

Summary

This study is being conducted to compare the safety and efficacy of icatibant with placebo in the treatment for Angiotensin-Converting Enzyme Inhibitor (ACE-I)-Induced Angioedema in Adults.

Clinical Details

Official title: Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study Evaluating the Safety & Efficacy of Icatibant as a Treatment for Angiotensin-Converting Enzyme Inhibitor (ACE-I)-Induced Angioedema in Adults

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Time to Meeting Discharge Criteria (TMDC).

Safety and tolerability of Icatibant.

Secondary outcome: Time to Onset of Symptom Relief (TOSR).

Occurrence of airway intervention due to ACE-I-induced angioedema.

Admission to the hospital or intensive care unit (ICU).

Angioedema attack following study drug administration.

Time to meeting discharge criteria (TMDC).

Detailed description: Angiotensin-converting enzyme inhibitors (ACE-Is) are the class of medications prescribed most frequently for the treatment of hypertension. They are also used post myocardial infarction as well as in patients with heart failure, diabetes mellitus, and chronic kidney disease. Approximately 35 to 40 million patients are on ACE-Is worldwide. Study HGT-FIR-096 is a multicenter, Phase III, randomized, double-blind, two-armed, placebo-controlled trial. The study population will consist of 118 adult patients, 18 years of age or older, who present with an acute ACE-I-induced angioedema attack. The primary aim of the study is to demonstrate that icatibant is significantly more effective than placebo in resolving attacks of angioedema caused by ACE-I based on the Time to Meeting Discharge Criteria (TMDC). Safety and tolerability, as well as the pharmacokinetics (PK), of icatibant will also be evaluated. Eligible patients will be randomized at a 1: 1 ratio to receive a single sub-cutaneous injection of either 30 mg icatibant or placebo.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria: Inclusion Criteria: 1. Male or female, 18 years of age or older. 2. Patient is currently being treated with an ACE inhibitor. 3. Patient presenting with an ACE inhibitor-induced angioedema attack of the head and/or neck region within 12 hours of onset (must be sufficiently less than 12 hours to allow study drug to be given with 12 hours of attack onset). 4. Angioedema must be considered at least moderate in severity for at least one of the four angioedema-associated airway symptoms (difficulty breathing, difficulty swallowing, voice changes, tongue swelling). 5. Patient must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient. 6. Females must have a negative urine pregnancy test prior to administration of the study medication, with the exception of those females who have had a total hysterectomy or bilateral oophorectomy, or who are 2 years post-menopausal. Exclusion Criteria: 1. Patient has a diagnosis of angioedema of other etiology (eg, hereditary or acquired angioedema, allergic angioedema [eg, food, insect bite or sting, evident clinical response to antihistamines and/or corticosteroids], anaphylaxis, trauma, abscess or infection or associated disease, local inflammation, local tumor, post-operative or post-radiogenic edema, salivary gland disorders, other [non-ACE inhibitor] drug-induced angioedema). 2. Patients with a family history of recurrent angioedema. 3. Patients who have had a previous episode(s) of angioedema while not on ACE inhibitor therapy. 4. Patients with acute urticaria (itchy, erythematous wheals). 5. Patients who have an intervention to support the airway (eg, intubation, tracheotomy, cricothyrotomy) due to the current attack of angioedema. 6. Patient has any of the following vascular conditions that, in the judgment of the investigator, would be a contraindication to participation in the study.

- Unstable angina pectoris or acute myocardial ischemia

- Hypertensive urgency or emergency (diastolic blood pressure [DBP] >120 mm Hg or

systolic blood pressure [SBP] >180 mm Hg)

- Within 1 month of a stroke or transient ischemic attack

- New York Heart Association (NYHA) heart failure class IV

7. Patient has a serious or acute condition or illness that, in the judgment of the investigator, would interfere with evaluating the safety and/or efficacy assessments of the study (eg, a condition or illness requiring hemodialysis). 8. Patient is pregnant or breast feeding. 9. Patient has participated in another investigational study in the past 30 days. 10. Patient is unable to understand the nature, scope, and possible consequences of the protocol, or is unlikely or unable to comply with the protocol assessments, or is unlikely to complete the study for any reason. 11. Patients who are not suitable for the study in the opinion of the investigator. 12. Patient has experienced hypersensitivity to the active substance of the investigational product or to any of its excipients.

Locations and Contacts

ShireHGT Call Center, Phone: +1-866-842-5335, Email: US_ShireHGT_Medicalinformation@shire. com Hals - Nasen - Ohrenklinik und Poliklinik, Munich 81675, Germany; Withdrawn

Klinik fГјr Hals-, Nasen - und Ohrenheilkunde, Ulm 89075, Germany; Withdrawn

Soroka University Medical Center, Beer Sheva 84101, Israel; Recruiting

Rita Troitsa, Phone: +97286244245, Email: ritaTr@clalit. org. il

Carmi Bartal, MD, Principal Investigator

Bnai Zion Medical Center, Haifa 31048, Israel; Recruiting

Regina Peri, Phone: +97248359659, Email: regina. peri@b-zion. org. il

Elias Toubi, MD, Principal Investigator

Ziv Medical Center, Safed 13100, Israel; Recruiting

Karina Shestatski, Phone: +97246828114, Email: clinical@ziv. health. gov. il

Osamah Hussein, MD, Principal Investigator

Tel-Aviv Sourasky Medical Center, Tel Aviv 64239, Israel; Recruiting

Dania Dror, Phone: +972524498779, Email: daniadror@gmail. com

Shmuel Kivity, MD, Principal Investigator

Brighton and Sussex University Hospitals NHS Trust, Brighton BN2 5BE, United Kingdom; Recruiting

Manchester Royal Infirmary, Manchester M13 9WL, United Kingdom; Recruiting

Rachel Pearson, Phone: +441612766777, Email: rachel. pearson2@cmft. nhs. uk

Richard Body, MD, Principal Investigator

Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom; Recruiting

Philip Miller, Phone: +441159249924, Ext: 67898, Email: philip. miller@nuh. nhs. uk

Christopher Gough, MD, Principal Investigator

University of California San Diego, La Jolla, California 92093, United States; Recruiting

Jennifer Blair, Phone: 858-822-6599, Email: jcblair@ucsd. edu

Marc Riedl, MD, Principal Investigator

University of California San Diego Medical Center, LaJolla, California 92037, United States; Recruiting

Jill Nyland, Phone: 224-610-1310, Email: jill. nyland@va. gov

Rohit Arora, MD, Principal Investigator

Saint Francis Medical Center, Peoria, Illinois 61606, United States; Withdrawn

University of Kansas Cancer Center, Kansas City, Kansas 66160, United States; Recruiting

Jeanie Whipple, Phone: 913-588-4643, Email: jwhipple@kumc. edu

Chris Cannon, MD, Principal Investigator

Ochsner Medical Center, New Orleans, Louisiana 70121, United States; Recruiting

Kelly Boudet, Phone: 504-842-5257, Email: kboudet@ochsner. org

Eiman Jahangir, MD, Principal Investigator

Louisiana State University Health Science Center, New OrlГ©ans, Louisiana 70070, United States; Withdrawn

Brigham and Womens Hospital, Boston, Massachusetts 02115, United States; Recruiting

Marian Tilearcio, Phone: 617-732-5638, Email: mtilearcio@partners. org

Daniel Pallin, MD, Principal Investigator

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting

Matthew Iandoli, Phone: 617-724-1714, Email: miandoli@mgh. harvard. edu

Aleena Banerji, MD, Principal Investigator

Baystate Medical Center, Springfield, Massachusetts 01199, United States; Recruiting

Kye Poronsky, BS, Phone: 413-794-4421, Email: kye. poronsky@baystatehealth. org

Howard Smithline, MD, Principal Investigator

Detroit Receiving Hospital and University Health Center, Detroit, Michigan 48201, United States; Recruiting

Temple University Hospital, Philadelphia, Pennsylvania 19140, United States; Recruiting

Patricia McNelis, Phone: 215-707-2235, Email: patricia. mcnelis@tuhs. temple. edu

Megan Healy, MD, Principal Investigator

Allegheny General Hospital, Pittsburgh, Pennsylvania 15143, United States; Recruiting

SueAnn Livingston, Phone: 412-359-8763, Email: saliving@wpahs. org

Arvind Venkat, MD, Principal Investigator

Rhode Island Hospital, Providence, Rhode Island 02903, United States; Recruiting

Karina Bertsch, CCRP, Phone: 401-444-9264, Email: kbertsch@lifespan. org

Gregory Jay, MD, Principal Investigator

University of South Carolina School of Medicine, Columbia, South Carolina 29203, United States; Recruiting

By Steven Bratman, M. D.

I once took alternative medicine on faith. For decades, I practiced it on patients and myself and my family, and assumed that pretty much all of it worked. Then I learned about double-blind studies, and it was like a tornado blowing down a house of cards. I discovered that I, like most people who love alternative medicine, had made a huge (though understandable) mistake.

Steven Bratman, M. D.

I had thought it was possible to know whether a treatment worked by trying it. I had also thought I could trust tradition, anecdote, and authority. I now see otherwise. The insights of the double-blind trial have cut through my wishful thinking and idealism, and turned me into a hard-nosed skeptic. Show me the double-blind studies, and I’ll pay attention. Otherwise, so far as I’m concerned, it’s little more than hot air.

Warning: This isn’t an easy subject. But if you read this through, and think about it, you will never look at alternative medicine (or any form of medicine) the same way again.

Placebo

A placebo is the term for a dummy drug, ie something that looks, smells and tastes like the compound or intervention that is being studied, but which has no active ingredient.

Using a placebo helps find out whether the active drug is really active. It also helps interpret side effects.

If 10% of people in the active drug group report having a headache and 2% of people in the placebo group report a headache, then it is reasonable to think that the active drug can cause headaches.

If 10% of the placebo group also reported a headache, then it is reasonable to think that the active drug doesn’t cause a headache.

An example of why placebo studies are still important was shown in the development of capravirine (an NNRTI). In a Phase IIb study people using capravirie plus a background combination did no better than people using the same regimen plus a placebo.

This stopped further development of the study drug. It protected other patients being put at risk from using an ineffective treatment in later trials.

Blind and double-blind studies

Blinding (sometimes called ‘masking’) is the term to describe a doctor, patient or researcher not knowing which study group a patient has been assigned to.

A blinded study is where the patient doesn’t know which group they are in, or which treatment they are getting.

A double-blinded study is where neither the doctor nor the patient know which group the patient is in.

Blinding prevents different care or treatment being given based on the personal beliefs of either the doctor or patient.

An example of why blinding is important is that if someone know they are getting an active drug, both doctors and patients may be more likely to report side effects.

It could also affect how often a patient takes the treatment.