Clinical trial NCT03020719: The Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Growth Parameters
Cystic Fibrosis
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2017-01-13
Enrollment: 60
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in Weight-for-age Z-score
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Change in Height-for-age Z-score
timeFrame: Baseline to 24 weeks
measure: Change in BMI-for-age Z-score
timeFrame: Baseline to 24 weeks
measure: Change in Fecal Calprotectin
timeFrame: Baseline to 24 weeks
measure: Change in High-sensitivity C-reactive Protein (Hs-CRP)
timeFrame: Baseline to 24 weeks
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline to 24 weeks
measure: Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline to 24 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Childrens Medical Center
state: Connecticut
city: Jacksonville
country: United States
facility: Nemours Childrens Clinic
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: Detroit
country: United States
facility: Childrens Hospital of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Women and Childrens Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Kansas City
country: United States
facility: The Childrens Mercy Hospital
state: Missouri
city: Buffalo
country: United States
facility: Women and Childrens Hospital of Buffalo
state: New York
city: New York
country: United States
facility: Childrens Hospital of New York/Columbia University Medical Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Inc.
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Milwaukee
country: United States
facility: Childrens Hospital of Milwaukee
state: Wisconsin
Study officials:
affiliation: University of Minnesota
name: Sarah J Schwarzenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University School of Medicine Riley Hospital
name: Molly Bozic, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.