Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis Patients

Cystic Fibrosis Clinical Trial

Official title:

Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis for Growth Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02029521
• Other study ID #: FIMP/clin.stud/2010/1.
• Status: Completed
• Phase: N/A
• First received: December 30, 2013
• Last updated: January 16, 2016
• Start date: March 2011
• Est. completion date: July 2012

Study information

• Verified date: January 2016
• Source: Brigham Young University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Federazione Italiana Medici Pediatri (Verbano Cusio Ossola)
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: July 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Months to 10 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Dietary Supplement:
• Oral reduced l-glutathione
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.
• Placebo
calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Clark Bishop

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight Percentile at 3 Months	Weight Percentile at 3 months adjusted for sex and age	3 months	No
Primary	Height Percentile	Height Percentile adjusted for sex and age	3 months	No
Primary	BMI Percentile	Body Mass Index percentile adjusted for sex and age. Standard BMI are not available for participants under 2 years of age	3 months	No
Primary	BMI Percentile	Body Mass Index percentile adjusted for sex and age. Not available for participants under 2 years of age.	6 months	No
Primary	Weight Percentile	Weight percentile, adjusted for sex and age	6 months	No
Primary	Height Percentile	The subjects were measured over the course of the study to determine if treatment improved height percentile.	6 Months	No
Primary	Fecal Calprotectin	Fecal Calprotectin, a measure of gut inflammation, was measured to see if the treatment decreased this outcome.	6 months	No
Secondary	Forced Vital Capacity	Forced vital capacity percent predicted	3 months	No
Secondary	FEV1	Forced expiratory volume at one second, percent predicted	3 months	No
Secondary	Bacteriology	Expectorated sputum or throat swab	3 months	No
Secondary	Forced Vital Capacity	Percent predicted of forced vital capacity.	6 months	No
Secondary	FEV1	Forced expiratory volume at one second, percent predicted.	6 months	No
Secondary	C-Reactive Protein (CRP)	CRP was measured to determine if this test fell during the course of treatment.	6 months	No
Secondary	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.	6 months	No
Secondary	Vitamin E	Serum Vitamin E levels were measured to determine if treatment affected this test.	6 months	No
Secondary	Alanine Aminotransferase (ALT)	ALT was measured to determine if liver function was affected by treatment over the course of the study.	6 Months	No
Secondary	Bacteriology	Expectorated sputum or throat swab	6 Months	No
Secondary	Frequency of Abdominal Pain	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Abdominal Pain	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Belching	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Belching	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Flatulence	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Flatulence	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Lack of Appetite	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Lack of Appetite	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Bloating	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Bloating	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Nausea	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Nausea	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Vomiting	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Vomiting	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Heart Burn	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Heart Burn	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Diarrhea	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Diarrhea	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of More Than 2 Bowel Movements Per Day	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of More Than 2 Bowel Movements Per Day	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No
Secondary	Frequency of Less Than 2 Bowel Movements Per Week	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent	6 months	No
Secondary	Severity of Less Than 2 Bowel Movements Per Week	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe	6 months	No