Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis Patients

N/ACompletedNCT02029521

Clark Bishop47 enrolled

Overview

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.

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.

Eligibility

Sex: ALLMin age: 18 MonthsMax age: 10 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Weight Percentile at 3 Months

Weight Percentile at 3 months adjusted for sex and age

Time frame: 3 months

Height Percentile

Height Percentile adjusted for sex and age

Time frame: 3 months

BMI Percentile

Body Mass Index percentile adjusted for sex and age. Standard BMI are not available for participants under 2 years of age

Time frame: 3 months

BMI Percentile

Body Mass Index percentile adjusted for sex and age. Not available for participants under 2 years of age.

Time frame: 6 months

Weight Percentile

Weight percentile, adjusted for sex and age

Time frame: 6 months

Height Percentile

The subjects were measured over the course of the study to determine if treatment improved height percentile.

Time frame: 6 Months

Fecal Calprotectin

Fecal Calprotectin, a measure of gut inflammation, was measured to see if the treatment decreased this outcome.

Time frame: 6 months

Secondary Outcomes

Forced Vital Capacity

Forced vital capacity percent predicted

Time frame: 3 months

FEV1

Forced expiratory volume at one second, percent predicted

Time frame: 3 months

Bacteriology

Expectorated sputum or throat swab

Time frame: 3 months

Forced Vital Capacity

Percent predicted of forced vital capacity.

Time frame: 6 months

FEV1

Forced expiratory volume at one second, percent predicted.

Time frame: 6 months

C-Reactive Protein (CRP)

CRP was measured to determine if this test fell during the course of treatment.

Time frame: 6 months

White Blood Cell Count

White blood cell count was measure at the beginning and end of the study to determine if treatment affected this test.

Time frame: 6 months

Vitamin E

Serum Vitamin E levels were measured to determine if treatment affected this test.

Time frame: 6 months

Alanine Aminotransferase (ALT)

ALT was measured to determine if liver function was affected by treatment over the course of the study.

Time frame: 6 Months

Bacteriology

Expectorated sputum or throat swab

Time frame: 6 Months

Frequency of Abdominal Pain

Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

Time frame: 6 months

Severity of Abdominal Pain