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Completed

NCT Number: NCT02029521

Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis Patients

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.

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Failure to Thrive Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Signs and Symptoms

Age range

18 month–10 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Turin, Italy

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Oral reduced l-glutathione

Dietary Supplement

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

Dietary Supplement

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 outcomes

  1. Weight Percentile at 3 Months

    Time frame: 3 months

    Weight Percentile at 3 months adjusted for sex and age

  2. Height Percentile

    Time frame: 3 months

    Height Percentile adjusted for sex and age

  3. BMI Percentile

    Time frame: 3 months

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

  4. BMI Percentile

    Time frame: 6 months

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

  5. Weight Percentile

    Time frame: 6 months

    Weight percentile, adjusted for sex and age

  6. Height Percentile

    Time frame: 6 Months

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

  7. Fecal Calprotectin

    Time frame: 6 months

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

Secondary outcomes

  1. Forced Vital Capacity

    Time frame: 3 months

    Forced vital capacity percent predicted

  2. FEV1

    Time frame: 3 months

    Forced expiratory volume at one second, percent predicted

  3. Bacteriology

    Time frame: 3 months

    Expectorated sputum or throat swab

  4. Forced Vital Capacity

    Time frame: 6 months

    Percent predicted of forced vital capacity.

  5. FEV1

    Time frame: 6 months

    Forced expiratory volume at one second, percent predicted.

  6. C-Reactive Protein (CRP)

    Time frame: 6 months

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

  7. White Blood Cell Count

    Time frame: 6 months

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

  8. Vitamin E

    Time frame: 6 months

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

  9. Alanine Aminotransferase (ALT)

    Time frame: 6 Months

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

  10. Bacteriology

    Time frame: 6 Months

    Expectorated sputum or throat swab

  11. Frequency of Abdominal Pain

    Time frame: 6 months

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

  12. Severity of Abdominal Pain

    Time frame: 6 months

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

  13. Frequency of Belching

    Time frame: 6 months

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

  14. Severity of Belching

    Time frame: 6 months

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

  15. Frequency of Flatulence

    Time frame: 6 months

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

  16. Severity of Flatulence

    Time frame: 6 months

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

  17. Frequency of Lack of Appetite

    Time frame: 6 months

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

  18. Severity of Lack of Appetite

    Time frame: 6 months

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

  19. Frequency of Bloating

    Time frame: 6 months

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

  20. Severity of Bloating

    Time frame: 6 months

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

  21. Frequency of Nausea

    Time frame: 6 months

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

  22. Severity of Nausea

    Time frame: 6 months

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

  23. Frequency of Vomiting

    Time frame: 6 months

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

  24. Severity of Vomiting

    Time frame: 6 months

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

  25. Frequency of Heart Burn

    Time frame: 6 months

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

  26. Severity of Heart Burn

    Time frame: 6 months

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

  27. Frequency of Diarrhea

    Time frame: 6 months

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

  28. Severity of Diarrhea

    Time frame: 6 months

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

  29. Frequency of More Than 2 Bowel Movements Per Day

    Time frame: 6 months

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

  30. Severity of More Than 2 Bowel Movements Per Day

    Time frame: 6 months

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

  31. Frequency of Less Than 2 Bowel Movements Per Week

    Time frame: 6 months

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

  32. Severity of Less Than 2 Bowel Movements Per Week

    Time frame: 6 months

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

Sponsors and collaborators

Lead sponsor

Clark Bishop

Other

Registry information

Official study title

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

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Jan 8, 2014
Registry last updated
Feb 8, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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