The Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis (GROW)
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Oral Glutathione
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Cystic Fibrosis focused on measuring Growth Parameters, Cystic Fibrosis
Eligibility Criteria
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
Sites / Locations
- Childrens Hospital Colorado
- Connecticut Childrens Medical Center
- Nemours Childrens Clinic
- Nemours Children's Clinic
- Emory University Hospital
- Riley Children's Hospital
- Childrens Hospital of Michigan
- Helen DeVos Women and Childrens Center
- University of Minnesota Medical Center
- The Childrens Mercy Hospital
- Women and Childrens Hospital of Buffalo
- Childrens Hospital of New York/Columbia University Medical Center
- Oregon Health & Science University
- UT Southwestern Medical Center
- Baylor College of Medicine
- The University of Vermont Inc.
- University of Virginia Health System
- Childrens Hospital of Milwaukee
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Oral Glutathione
Placebo
Arm Description
Oral Glutathione oral powder at 65mg/kg/day
Placebo oral powder at 65mg/kg/day
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Change in Fecal Calprotectin
Difference between the oral glutathione and placebo groups in the 24-week change from baseline in fecal calprotectin.
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.
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.
Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Rate is defined as the number of events per participant follow-up month.
Full Information
NCT ID
NCT03020719
First Posted
January 11, 2017
Last Updated
December 20, 2019
Sponsor
University of Minnesota
Collaborators
Cystic Fibrosis Foundation
1. Study Identification
Unique Protocol Identification Number
NCT03020719
Brief Title
The Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis
Acronym
GROW
Official Title
A Multi Center Placebo Controlled Double Blind Randomized Study Evaluating the Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
June 14, 2017 (Actual)
Primary Completion Date
December 12, 2018 (Actual)
Study Completion Date
December 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
Collaborators
Cystic Fibrosis Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Growth Parameters, Cystic Fibrosis
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oral Glutathione
Arm Type
Experimental
Arm Description
Oral Glutathione oral powder at 65mg/kg/day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo oral powder at 65mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Oral Glutathione
Other Intervention Name(s)
GSH
Intervention Description
Oral Glutathione oral powder
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Inactive powder
Intervention Description
Placebo oral powder
Primary Outcome Measure Information:
Title
Change in Weight-for-age Z-score
Description
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.
Time Frame
Baseline to 24 weeks
Secondary Outcome Measure Information:
Title
Change in Height-for-age Z-score
Description
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.
Time Frame
Baseline to 24 weeks
Title
Change in BMI-for-age Z-score
Description
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.
Time Frame
Baseline to 24 weeks
Title
Change in Fecal Calprotectin
Description
Difference between the oral glutathione and placebo groups in the 24-week change from baseline in fecal calprotectin.
Time Frame
Baseline to 24 weeks
Title
Change in High-sensitivity C-reactive Protein (Hs-CRP)
Description
Difference between the oral glutathione and placebo groups in the 24-week change from baseline in hs-CRP.
Time Frame
Baseline to 24 weeks
Title
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
The number and percentage of participants with at least one event over the 24 week follow-up period.
Time Frame
Baseline to 24 weeks
Title
Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
Rate is defined as the number of events per participant follow-up month.
Time Frame
Baseline to 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarah J Schwarzenberg, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Molly Bozic, MD
Organizational Affiliation
Indiana University School of Medicine Riley Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Childrens Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Connecticut Childrens Medical Center
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06107
Country
United States
Facility Name
Nemours Childrens Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Nemours Children's Clinic
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30324
Country
United States
Facility Name
Riley Children's Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Childrens Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Helen DeVos Women and Childrens Center
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
University of Minnesota Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55414
Country
United States
Facility Name
The Childrens Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Women and Childrens Hospital of Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14222
Country
United States
Facility Name
Childrens Hospital of New York/Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The University of Vermont Inc.
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Childrens Hospital of Milwaukee
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32960827
Citation
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.
Results Reference
derived
Learn more about this trial
The Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis
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