Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis Patients

Not Applicable

Completed

Conditions: Cystic Fibrosis

Interventions: Dietary Supplement: Oral reduced l-glutathione
Dietary Supplement: Placebo

Registration Number: NCT02029521

Lead Sponsor: Clark Bishop

Brief Summary: Many individuals with cystic fibrosis experience growth failure. The reasons are not clear, but inflammation of the gut in these patients seems to be one important reason. Glutathione is important to normal function of the intestine and lungs. Glutathione functions to decrease inflammation and to thin mucus. However, in cystic fibrosis, glutathione gets trapped inside of cells, so it cannot travel to the surface of the cells and perform its proper function. Moreover, glutathione has been shown to improve nutritional status in patients with AIDS and cancer.

Investigators hypothesize that supplementation of oral glutathione to pediatric individuals with cystic fibrosis could improve growth failure.

Detailed Description: Cystic fibrosis (CF) is known principally for its pulmonary consequences. However, for most individuals with CF, the earliest manifestations are not pulmonary, but gastro-intestinal. Many children experience growth failure. Chronic gut inflammation also develops. Research has also established that lung function scores are significantly correlated with Body Mass Index (BMI) and weight percentile in CF. Therefore, interventions to improve the gastro-intestinal dimension of CF in early childhood have the potential to ameliorate the course of the disease over the life span of the patient. Both Cochrane Database reviews and a recent review commissioned by the Cystic Fibrosis Foundation found only fair evidence for current nutritional guidelines.Therefore, there is a pressing need for a treatment for CF growth failure that is more effective and less invasive than current treatments.

The discovery that CF is associated with significantly diminished efflux of reduced glutathione (GSH) from most cells in the body offers a new perspective on the pathophysiology of this disease. GSH plays several important roles; among the most important are the following: 1) primary water-soluble antioxidant; 2) mucolytic capable of cleaving disulfide bonds; and 3) regulator of immune system function. The relationship between redox ratio (GSH:GSSG) and total glutathione (GSH+GSSG) and the initiation of inflammation is well established in the research literature.

GSH is also an important component of the epithelial lining fluid of the intestines, helping to keep intestinal mucus thin, serving to defend the intestinal system against reactive oxygen species, and keeping inflammation in check under normal circumstances. GSH is an FDA-approved treatment for AIDS-related cachexia. The growing recognition of GSH system dysfunction in CF, coupled with an established research literature on the role of GSH in gastro-intestinal function and weight gain in non-CF contexts, suggest a new intervention for growth failure in early childhood in CF patients. Specifically, investigators hypothesized that oral glutathione could effectively treat CF growth failure in pediatric patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

Inclusion Criteria

-Diagnosis of Cystic Fibrosis by either of the following criteria: >60 sweat chloride test or paired deleterious DNA cystic fibrosis transmembrane conductance regulator (CFTR) mutations (Ambry genetics, Genetech or ARUP);

-Pancreatic insufficient as defined by doctor's prescription of pancreatic enzymes.

Exclusion Criteria

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,
who had been taking either GSH or N-acetyl cysteine (NAC) within the 12 month period immediately prior to the trial,
chronically infected with Burkholderia cepacia.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral reduced l-glutathione	Oral reduced l-glutathione	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg.
Placebo Calcium Citrate	Placebo	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.

Primary Outcome Measures

Name	Time	Method
Weight Percentile at 3 Months	3 months	Weight Percentile at 3 months adjusted for sex and age
Height Percentile	6 Months	The subjects were measured over the course of the study to determine if treatment improved height percentile.
BMI Percentile	6 months	Body Mass Index percentile adjusted for sex and age. Not available for participants under 2 years of age.
Weight Percentile	6 months	Weight percentile, adjusted for sex and age
Fecal Calprotectin	6 months	Fecal Calprotectin, a measure of gut inflammation, was measured to see if the treatment decreased this outcome.

Secondary Outcome Measures

Name	Time	Method
Bacteriology	6 Months	Expectorated sputum or throat swab
Severity of Flatulence	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Forced Vital Capacity	6 months	Percent predicted of forced vital capacity.
Frequency of Lack of Appetite	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
White Blood Cell Count	6 months	White blood cell count was measure at the beginning and end of the study to determine if treatment affected this test.
FEV1	6 months	Forced expiratory volume at one second, percent predicted.
C-Reactive Protein (CRP)	6 months	CRP was measured to determine if this test fell during the course of treatment.
Vitamin E	6 months	Serum Vitamin E levels were measured to determine if treatment affected this test.
Alanine Aminotransferase (ALT)	6 Months	ALT was measured to determine if liver function was affected by treatment over the course of the study.
Frequency of Abdominal Pain	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of Abdominal Pain	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Frequency of Belching	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of Belching	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Severity of Bloating	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Frequency of Flatulence	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of Lack of Appetite	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Frequency of Bloating	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Frequency of Nausea	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of Nausea	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Frequency of Vomiting	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of Vomiting	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Frequency of Heart Burn	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of Heart Burn	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Frequency of Diarrhea	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of Diarrhea	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Frequency of More Than 2 Bowel Movements Per Day	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of More Than 2 Bowel Movements Per Day	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Frequency of Less Than 2 Bowel Movements Per Week	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Severity of Less Than 2 Bowel Movements Per Week	6 months	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe