Clinical trial NCT02029521: Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis Patients
Official title: Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis for Growth Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
growth Failure
glutathione
Lead sponsor: Brigham Young University
Sponsor class: OTHER
First posted: 2014-01-08
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Weight Percentile at 3 Months
timeFrame: 3 months
measure: Height Percentile
timeFrame: 3 months
measure: BMI Percentile
timeFrame: 3 months
measure: BMI Percentile
timeFrame: 6 months
measure: Weight Percentile
timeFrame: 6 months
measure: Height Percentile
timeFrame: 6 Months
measure: Fecal Calprotectin
timeFrame: 6 months
Secondary outcomes:
measure: Forced Vital Capacity
timeFrame: 3 months
measure: FEV1
timeFrame: 3 months
measure: Bacteriology
timeFrame: 3 months
measure: Forced Vital Capacity
timeFrame: 6 months
measure: FEV1
timeFrame: 6 months
measure: C-Reactive Protein (CRP)
timeFrame: 6 months
measure: White Blood Cell Count
timeFrame: 6 months
measure: Vitamin E
timeFrame: 6 months
measure: Alanine Aminotransferase (ALT)
timeFrame: 6 Months
measure: Bacteriology
timeFrame: 6 Months
measure: Frequency of Abdominal Pain
timeFrame: 6 months
measure: Severity of Abdominal Pain
timeFrame: 6 months
measure: Frequency of Belching
timeFrame: 6 months
measure: Severity of Belching
timeFrame: 6 months
measure: Frequency of Flatulence
timeFrame: 6 months
measure: Severity of Flatulence
timeFrame: 6 months
measure: Frequency of Lack of Appetite
timeFrame: 6 months
measure: Severity of Lack of Appetite
timeFrame: 6 months
measure: Frequency of Bloating
timeFrame: 6 months
measure: Severity of Bloating
timeFrame: 6 months
measure: Frequency of Nausea
timeFrame: 6 months
measure: Severity of Nausea
timeFrame: 6 months
measure: Frequency of Vomiting
timeFrame: 6 months
measure: Severity of Vomiting
timeFrame: 6 months
measure: Frequency of Heart Burn
timeFrame: 6 months
measure: Severity of Heart Burn
timeFrame: 6 months
measure: Frequency of Diarrhea
timeFrame: 6 months
measure: Severity of Diarrhea
timeFrame: 6 months
measure: Frequency of More Than 2 Bowel Movements Per Day
timeFrame: 6 months
measure: Severity of More Than 2 Bowel Movements Per Day
timeFrame: 6 months
measure: Frequency of Less Than 2 Bowel Movements Per Week
timeFrame: 6 months
measure: Severity of Less Than 2 Bowel Movements Per Week
timeFrame: 6 months
Other outcomes:
Locations:
city: Turin
country: Italy
Study officials:
affiliation: Intermountain Health Care
name: Clark T Bishop, MD
role: STUDY_DIRECTOR
References: