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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Oral Glutathione; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Childrens Hospital Colorado
  • Connecticut
    • Hartford, Connecticut, United States, 06107
      • Connecticut Childrens Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Childrens Clinic
    • Pensacola, Florida, United States, 32504
      • Nemours Children's Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30324
      • Emory University Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Children's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Childrens Hospital of Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Women and Childrens Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University Of Minnesota Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • The Childrens Mercy Hospital
  • New York
    • Buffalo, New York, United States, 14222
      • Women and Childrens Hospital of Buffalo
    • New York, New York, United States, 10032
      • Childrens Hospital of New York/Columbia University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Inc.
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Childrens Hospital of Milwaukee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female ≥ 2 and < 11 years of age at Visit 1
2. 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
3. Weight-for-age between the 10th and 50th percentiles at Screening (Visit 1) (using the Center for Disease Control (CDC) reference equations)
4. Current chronic use, greater than 8 weeks before Day 0, of pancreatic enzyme replacement therapy (PERT) for management of pancreatic insufficiency
5. 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
6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Oral Glutathione; Oral Glutathione oral powder at 65mg/kg/day	Drug: Oral Glutathione; Oral Glutathione oral powder; Other Names: GSH
PLACEBO_COMPARATOR: Placebo; Placebo oral powder at 65mg/kg/day	Drug: Placebo; Placebo oral powder; Other Names: Inactive powder

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Sarah J Schwarzenberg, MD, University of Minnesota; Principal Investigator: Molly Bozic, MD, Indiana University School of Medicine Riley Hospital

Publications and helpful links

General Publications

• Bozic M, Goss CH, Tirouvanziam RM, Baines A, Kloster M, Antoine L, Borowitz D, Schwarzenberg SJ; GROW study group. Oral Glutathione and Growth in Cystic Fibrosis: A Multicenter, Randomized, Placebo-controlled, Double-blind Trial. J Pediatr Gastroenterol Nutr. 2020 Dec;71(6):771-777. doi: 10.1097/MPG.0000000000002948.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2017
• Primary Completion (ACTUAL): December 12, 2018
• Study Completion (ACTUAL): December 12, 2018

Study Registration Dates

• First Submitted: January 11, 2017
• First Submitted That Met QC Criteria: January 12, 2017
• First Posted (ESTIMATE): January 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 9, 2020
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Growth Parameters
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: GROW-IP-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No