Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis Patients
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional

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.
    

Intervention name(s): Oral reduced l-glutathione; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. 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.; calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: cystic fibrosis; growth Failure; glutathione