Cystic FibrosisNCT02029521
Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis Patients
A study testing Oral reduced l-glutathione in people with Cystic Fibrosis, run by Clark Bishop at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 months to 10 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Oral reduced l-glutathione
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteItaly
- Study dates
- Mar 2011to Jul 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 months to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- -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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis for Growth Failure
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.
Read the detailed description
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.
- Conditions
- Cystic Fibrosis
- Being tested
- Oral reduced l-glutathione, Placebo
- Keywords
- cystic fibrosis, growth Failure, glutathione
- Medical subject headings
- Cystic Fibrosis, Failure to Thrive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral reduced l-glutathioneDietary 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.
PlaceboDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| Oral reduced l-glutathione | Experimental | The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Receives: Dietary Supplement: Oral reduced l-glutathione |
| Placebo Calcium Citrate | Placebo comparator | 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. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight Percentile at 3 Months
Weight Percentile at 3 months adjusted for sex and age
Measured: 3 months
Height Percentile
Height Percentile adjusted for sex and age
Measured: 3 months
BMI Percentile
Body Mass Index percentile adjusted for sex and age. Standard BMI are not available for participants under 2 years of age
Measured: 3 months
BMI Percentile
Body Mass Index percentile adjusted for sex and age. Not available for participants under 2 years of age.
Measured: 6 months
Weight Percentile
Weight percentile, adjusted for sex and age
Measured: 6 months
Height Percentile
The subjects were measured over the course of the study to determine if treatment improved height percentile.
Measured: 6 Months
Fecal Calprotectin
Fecal Calprotectin, a measure of gut inflammation, was measured to see if the treatment decreased this outcome.
Measured: 6 months
Secondary outcomes (32)
Forced Vital Capacity
Forced vital capacity percent predicted
Measured: 3 months
FEV1
Forced expiratory volume at one second, percent predicted
Measured: 3 months
Bacteriology
Expectorated sputum or throat swab
Measured: 3 months
Forced Vital Capacity
Percent predicted of forced vital capacity.
Measured: 6 months
FEV1
Forced expiratory volume at one second, percent predicted.
Measured: 6 months
C-Reactive Protein (CRP)
CRP was measured to determine if this test fell during the course of treatment.
Measured: 6 months
White Blood Cell Count
White blood cell count was measure at the beginning and end of the study to determine if treatment affected this test.
Measured: 6 months
Vitamin E
Serum Vitamin E levels were measured to determine if treatment affected this test.
Measured: 6 months
Alanine Aminotransferase (ALT)
ALT was measured to determine if liver function was affected by treatment over the course of the study.
Measured: 6 Months
Bacteriology
Expectorated sputum or throat swab
Measured: 6 Months
Frequency of Abdominal Pain
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Abdominal Pain
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Belching
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Belching
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Flatulence
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Flatulence
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Lack of Appetite
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Lack of Appetite
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Bloating
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Bloating
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Nausea
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Nausea
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Vomiting
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Vomiting
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Heart Burn
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Heart Burn
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Diarrhea
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Diarrhea
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of More Than 2 Bowel Movements Per Day
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of More Than 2 Bowel Movements Per Day
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Frequency of Less Than 2 Bowel Movements Per Week
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Measured: 6 months
Severity of Less Than 2 Bowel Movements Per Week
Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2014 (estimated)
- Study startMar 2011
- Primary completionMar 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clark Bishop
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Clark Bishop, Brigham Young University
- Investigators
- Clark T Bishop, MD, Study director, Intermountain Health Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02029521
- Sponsor's protocol ID
- FIMP/clin.stud/2010/1.
- Status last verified
- Jan 2016
- First submitted
- 30 Dec 2013
- Last updated
- 8 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis for Growth Failure
- ClinicalTrials.gov ID
- NCT02029521
- Acronym / sponsor ID
- FIMP/clin.stud/2010/1.
- Conditions
- Cystic Fibrosis
- Keywords
- cystic fibrosis, growth Failure, glutathione
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Clark BishopUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 8 Jan 2014 (estimated)
- Results
- Posted 21 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral reduced l-glutathione | Experimental | Dietary Supplement: Oral reduced l-glutathioneThe treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. |
| Placebo Calcium Citrate | Placebo comparator | Dietary Supplement: PlaceboThe 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. |
Who may qualify
- Ages
- 18 months to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- -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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral reduced l-glutathioneThe 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. | Dietary supplement | Oral reduced l-glutathione |
| Placebocalcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime. | Dietary supplement | Placebo Calcium Citrate |
Primary outcome
Weight Percentile at 3 Months
Time frame: 3 months
Weight Percentile at 3 months adjusted for sex and age
Height Percentile
Time frame: 3 months
Height Percentile adjusted for sex and age
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
BMI Percentile
Time frame: 6 months
Body Mass Index percentile adjusted for sex and age. Not available for participants under 2 years of age.
Weight Percentile
Time frame: 6 months
Weight percentile, adjusted for sex and age
Height Percentile
Time frame: 6 Months
The subjects were measured over the course of the study to determine if treatment improved height percentile.
Fecal Calprotectin
Time frame: 6 months
Fecal Calprotectin, a measure of gut inflammation, was measured to see if the treatment decreased this outcome.
32 secondary outcomes
Forced Vital Capacity
Time frame: 3 months
FEV1
Time frame: 3 months
Bacteriology
Time frame: 3 months
Forced Vital Capacity
Time frame: 6 months
FEV1
Time frame: 6 months
C-Reactive Protein (CRP)
Time frame: 6 months
White Blood Cell Count
Time frame: 6 months
Vitamin E
Time frame: 6 months
Alanine Aminotransferase (ALT)
Time frame: 6 Months
Bacteriology
Time frame: 6 Months
Frequency of Abdominal Pain
Time frame: 6 months
Severity of Abdominal Pain
Time frame: 6 months
Frequency of Belching
Time frame: 6 months
Severity of Belching
Time frame: 6 months
Frequency of Flatulence
Time frame: 6 months
Severity of Flatulence
Time frame: 6 months
Frequency of Lack of Appetite
Time frame: 6 months
Severity of Lack of Appetite
Time frame: 6 months
Frequency of Bloating
Time frame: 6 months
Severity of Bloating
Time frame: 6 months
Frequency of Nausea
Time frame: 6 months
Severity of Nausea
Time frame: 6 months
Frequency of Vomiting
Time frame: 6 months
Severity of Vomiting
Time frame: 6 months
Frequency of Heart Burn
Time frame: 6 months
Severity of Heart Burn
Time frame: 6 months
Frequency of Diarrhea
Time frame: 6 months
Severity of Diarrhea
Time frame: 6 months
Frequency of More Than 2 Bowel Movements Per Day
Time frame: 6 months
Severity of More Than 2 Bowel Movements Per Day
Time frame: 6 months
Frequency of Less Than 2 Bowel Movements Per Week
Time frame: 6 months
Severity of Less Than 2 Bowel Movements Per Week
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clark T Bishop, MD study director
Intermountain Health Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral reduced l-glutathione in people with Cystic Fibrosis, run by Clark Bishop at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight Percentile at 3 Months (time frame: 3 months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2016.