The Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis

Study Overview
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Brief Summary
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The purpose of this randomized, placebo-controlled (Phase II) study will be to further evaluate the effects of oral glutathione on growth in children with CF.

Detailed Description
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a prospective, multi-center, randomized, placebocontrolled, double-blind, Phase II clinical trial. Approximately sixty pancreatic insufficient (PI) subjects with CF who are ≥ 2 and < 11 years of age, will be enrolled to receive either L-Glutathione Reduced (GSH) or placebo given orally (tid) for 24 weeks. Each subject will be seen for four study visits: Visit 1 (Screening), Visit 2 (Baseline/Randomization, Day 0), Visit 3 (Week 12) and Visit 4 (Week 24). At Visit 2, subjects will be randomized to receive either active treatment or placebo. Visit 1 and 2 may be combined if subject meets eligibility requirements and a fecal specimen is collected prior to dosing. Safety and clinical outcomes will be assessed throughout the study. Assessment of inflammatory and other bio-markers in blood and fecal specimens will be performed at Visits 2 and 4

Official Title
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A Multi Center Placebo Controlled Double Blind Randomized Study Evaluating the Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Oral Glutathione
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 2 and < 11 years of age at Visit 1 Documentation of a CF diagnosis as evidenced by the following criteria: Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) AND Two well-characterized mutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene Weight-for-age between the 10th and 50th percentiles at Screening (Visit 1) (using the Center for Disease Control (CDC) reference equations) Current chronic use, greater than 8 weeks before Day 0, of pancreatic enzyme replacement therapy (PERT) for management of pancreatic insufficiency Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability to comply with the requirements of the study Clinically stable with no significant changes in health status within 2 weeks prior to Day 0 Exclusion Criteria: 1. Intestinal obstruction or gastrointestinal surgery within the 6 months prior to Day 0 2. History of diabetes, Crohn's disease, celiac disease, or bowel resection 3. Use of either oral or inhaled GSH or N-acetyl cysteine within the 4 months prior to Screening (Visit 1) 4. Known hypersensitivity to oral glutathione or lactose 5. Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline, azithromycin, Pulmozyme, Cayston TOBI Kalydeco,Orkambi, Proton Pump Inhibitor, Histamine H-2 Blocker [PPI/H2-blocker], Miralax® , PERT, dietary supplementation, probiotics) within the 4 weeks prior to Day 0 6. Changes in the amount of proprietary dietary supplement formulas (e.g., Scandishakes, Boost, Pediasure, or homemade formula) given (oral or gastrostomy tube) within the 4 weeks prior to Day 0 7. Use of antibiotics (oral, IV, or inhaled) for acute symptoms within the 2 weeks prior to Day 0 8. Use of oral steroids within the 4 weeks prior to Day 0 9. Active treatment for nontuberculous mycobacteria (NTM) at Day 0 10. Active treatment for allergic bronchopulmonary aspergillosis (ABPA) at Day 0 11. Administration of any investigational drug within the 30 days prior to Day 0 12. Sibling who received study drug as part of this study 13. Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the patient or the quality of the data

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Glutathione<br>Oral Glutathione oral powder at 65mg/kg/day | Drug: Oral Glutathione<br>* Oral Glutathione oral powder<br>* Other names: GSH;|
| Placebo Comparator: Placebo<br>Placebo oral powder at 65mg/kg/day | Drug: Placebo<br>* Placebo oral powder<br>* Other names: Inactive powder;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight-for-age Z-score | Difference between the oral glutathione and placebo groups in the 24-week change from baseline in weight-for-age Z-score. Weight-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Height-for-age Z-score | Difference between the oral glutathione and placebo groups in the 24-week change from baseline in height-for-age Z-score. Height-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline to 24 weeks | 
| Change in BMI-for-age Z-score | Difference between the oral glutathione and placebo groups in the 24-week change from baseline in BMI-for-age Z-score. BMI-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. | Baseline to 24 weeks | 
| Change in Fecal Calprotectin | Difference between the oral glutathione and placebo groups in the 24-week change from baseline in fecal calprotectin. | Baseline to 24 weeks | 
| Change in High-sensitivity C-reactive Protein (Hs-CRP) | Difference between the oral glutathione and placebo groups in the 24-week change from baseline in hs-CRP. | Baseline to 24 weeks | 
| Adverse Events (AEs) and Serious Adverse Events (SAEs) | The number and percentage of participants with at least one event over the 24 week follow-up period. | Baseline to 24 weeks | 
| Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Rate is defined as the number of events per participant follow-up month. | Baseline to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth Parameters, Cystic Fibrosis