Data and Supplementary Materials,
Visca et al 2012 Trial
These Data and Supplementary Materials are adjunct to the article,
Oral Reduced L-Glutathione Improves Nutritional Status and Fecal Calprotectin in Pediatric Cystic Fibrosis Patients: A Randomized, Double Blinded, Placebo-Controlled Clinical Trial
Authors: Alfredo Visca, Clark T. Bishop, Sterling C. Hilton, Valerie M. Hudson
FULL DATA SPREADSHEET: Download by clicking HERE
SUPPLEMENTARY MATERIALS
Additional Details on the Trial Protocol:
Inclusion/Exclusion Criteria: To be included, subjects had to have cystic fibrosis as measured by >60 sweat chloride test or paired deleterious DNA CFTR mutations (Ambry genetics, Genetech or ARUP); and had to be pancreatic insufficient as defined by doctor’s prescription of pancreatic enzymes. Subjects were excluded if they had been hospitalized for bowel obstruction or surgery in the six months prior to enrollment; had had a pulmonary exacerbation or oral steroid use or IV antibiotics within one month of enrollment, or who had been taking either GSH or NAC within the 12 month period immediately prior to the trial, or who were chronically infected with B. cepacia.
Informed Consent: Since the subjects of the clinical trial were small children, the parents and guardians were informed of the clinical trial, and if they expressed interest, the parents were provided a written document and oral explanation of the trial and its potential risks and benefits to participants. The trial protocol was also included. A letter from the enrolling physician was provided to the parents to give to their family doctor concerning the trial. If the parents continued to express interest in having their children participate in the trial, a written document in age-appropriate language was also provided to the older children, outlining the protocol, and potential risks and benefits to them. At that point, the parents (both father and mother) were asked to sign a formal informed consent form, and older children were also asked to sign an assent form that was written in age-appropriate language.
Sample Characteristics:
Size: Using data from a previously published study that included several patients that met our inclusion criteria [1], for the proposed study we purposed to enroll a minimum of 22 patients in each group. This would accommodate a 10% attrition rate and allow for the detection of an effect size of 8 percentage points with 90% power. An effect size of 8% is substantially smaller than that observed in the relevant patients in the previously published study; however, we reasoned that it was possible that the effect size would be smaller in the current trial due to the possibility of non-compliance and the unknown change in weight percentile in the control group over the six month period. This N-size would also be clinically relevant, and we deemed it feasible to enroll 44 patients from the available patient pool of subjects.
Age stratification: For the two age groups, we enrolled a minimum of 6 patients in the treatment group and 6 patients in the placebo group in the younger age group (ages 18 months to 3 years), and a minimum of 16 patients in the treatment group and 16 patients in the placebo group in the older age group (aged > 3 years). This was done so that results would not be influenced by differential age characteristics between the two groups.
Randomization: Once patients were enrolled, they were randomly assigned to treatment or placebo by use of a random number generator.
Miscellaneous Specifics:
1) Because of recruitment logistics, there were four possible start dates for the trial participants, i.e., March 1, 2011, May 2, 2011, July 1, 2011, or September 1, 2011.
2) A phone number was provided if the participants had any questions, concerns, or problems.
3) There were three formal visits with the study physician; baseline, three months, and six months. The physician also visited with the patients a month before the baseline measures were taken.
4) Other measures recorded included lung sounds as noted through stethoscope by the study physician.
5) Patients were asked about frequency and severity of the following gastro-intestinal symptoms over the course of the trial:
o Frequency and Severity of Abdominal Pain
o Frequency and Severity of Belching
o Frequency and Severity of Flatulence
o Frequency and Severity of Lack of Appetite
o Frequency and Severity of Bloating
o Frequency and Severity of Nausea
o Frequency and Severity of Vomiting
o Frequency and Severity of Heartburn
o Frequency and Severity of Diarrhea
o Frequency and Severity of Having More than Two Bowel Movements Per Day
o Frequency and Severity of Having Fewer than Two Bowel Movements Per Week
6) All recorded weights were confirmed with the patients’ parents after the conclusion of the trial.
7) In the GSH treatment group, 14 patients (63.6%) had at least one delF508 mutation, and in the placebo group, 15 patients (68.1%) had at least one delF508. In the GSH treatment group, 3 patients (13.6%) were homozygous for the delF508, and in the placebo group, 5 patients (27.7%) were homozygous for the delF508. Sweat chloride levels were not significantly different between the two groups.
Instruments:
Spirometric data were obtained using a micro loop pneumotachograph (Micro Medical Limited, UK), and predicted normal values for spirometric data were obtained from Knudson [2]. For percentile values on weight, height, and BMI, http://www.infantchart.com/child/ , accessed on June 2014, was used. We used WHO growth charts for children under 2 and CDC growth charts for children 2 and older. Weights were obtained using Kern scales (Model MPB300K100P) and Seca scales.
Materials: The treatment substance was pharmaceutical grade Reduced L-Glutathione (GSH), encapsulated and packaged by Theranaturals, Inc. The placebo substance was calcium citrate, encapsulated and packaged by Theranaturals, Inc. Treatment was administered in the form of 300 mg opaque capsules. Bottles were labeled only with “A” or “B,” in order to achieve double-blinding. Placebo will also be in opaque capsules, with number of milligrams determined by the encapsulator. All subjects were instructed to take 1/3 of their daily dose at mealtimes (breakfast, lunch, dinner). For children who could not yet swallow capsules, parents were instructed to stir the contents of the capsule into their children’s food (e.g. applesauce, cereal, etc.).
REFERENCES
[1] Visca A, Bishop CT, Hilton SC, Hudson VM. Improvement in clinical markers in CF patients using a reduced glutathione regimen: an uncontrolled, observational study. J Cyst Fibros. 2008 Sep;7(5):433-6.
[2] Knudson, RJ, et al. The Maximal Expiratory Flow-Volume Curve Normal Standards, Variability, and Effects of Age. Am Rev Respir Dis 113:589-590, 1976.