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Effect of Glycine in Cystic Fibrosis

This study has been terminated.
(Some of the researchers finished their participation in the study.)
Sponsor:
Collaborators:
Hospital Infantil de Mexico Federico Gomez
Instituto Mexicano del Seguro Social
Information provided by (Responsible Party):
Mario H. Vargas, Instituto Nacional de Enfermedades Respiratorias
ClinicalTrials.gov Identifier:
NCT01417481
First received: August 15, 2011
Last updated: October 30, 2014
Last verified: October 2014
  Purpose

The aim of this study is to evaluate if glycine, orally administered in a daily dose of 0.5 g/kg during 8 weeks, can ameliorate the airway inflammation in children with cystic fibrosis, as compared with placebo. During all of the study children will receive their usual treatment for cystic fibrosis.


Condition Intervention Phase
Cystic Fibrosis
Dietary Supplement: Glycine
Dietary Supplement: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of the Capability of a Glycine Oral Supplement for Diminishing Bronchial Inflammation in Children With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by Instituto Nacional de Enfermedades Respiratorias:

Primary Outcome Measures:
  • Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]). Then, percentages were log-transformed to adjust to a normal distribution.

  • Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]). Then, percentage change was log-transformed to adjust to a normal distribution.

  • Changes in Serum Concentration of Inflammatory Biomarkers (TNF-alpha) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]). Then, percentages were log-transformed to adjust to a normal distribution.

  • Changes in Sputum Concentration of Inflammatory Biomarkers (IL-6) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]). Then, percentage change was log-transformed to adjust to a normal distribution.

  • Changes in Sputum Concentration of Inflammatory Biomarkers (G-CSF) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]). Then, percentage change was log-transformed to adjust to a normal distribution.


Secondary Outcome Measures:
  • Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]).

    Each respiratory symptom (Cough severity, Sputum features, Appetite, Dyspnea, and Energy perception) was evaluated in a 5-options Likert scale, ranging from 1 (better) to 5 (worse). The total score was computed by the simple sum of the five symptoms.


  • Changes in Score for Sputum Production, Dyspnea and Global Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]).

    In the symptoms questionnaire, each respiratory symptom (Cough severity, Sputum features, Appetite, Dyspnea, and Energy perception) was evaluated in a 5-options Likert scale, ranging from 1 (better) to 5 (worse). The total score was computed by the simple sum of the five symptoms.


  • Changes in Pulse Oximetry, FEV1/FVC, and FEF50. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]).

  • Changes in FEV1, FEF25, and FEFmax [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]).

  • Changes in Other Spirometric Variables [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value [beginning of the glycine or placebo period, respectively]).


Enrollment: 13
Study Start Date: March 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Glycine
Patients will receive a daily oral supplement of 0.5 g/kg glycine dissolved in water.
Dietary Supplement: Glycine
Daily oral supplement of glycine at a dose of 0.5 g/kg divided in three doses during 8 weeks
Other Name: aminoacetic acid
Placebo Comparator: Placebo
Patients will receive a daily supplement of 0.5 g/kg sugar glass dissolved in water.
Dietary Supplement: Placebo
Daily oral administration of placebo (sugar glass) at a dose of 0.5 g/kg divided in three doses during 8 weeks
Other Name: sugar glass

  Hide Detailed Description

Detailed Description:

Background. Cystic fibrosis (CF) is a genetic disorder caused by a mutation in a gene that codifies for a chloride channel named "cystic fibrosis transmembrane regulator" (CFTR). In the lungs this results in thick and dehydrated mucus that tends to cause obstruction of the bronchial lumen. Neutrophils and proinflammatory substances have been detected in bronchoalveolar lavage fluid of children with CF who have no bacterial infection. This inflammation conditions a vicious circle in which airways are colonized by bacteria that further increase inflammation. Persistent inflammation leads to irreversible changes in airways, which become distorted. Therefore, a key step in CF treatment is reduction of airway inflammation, for which long-term use of corticosteroids, ibuprofen or macrolides may be indicated.

Glycine and its antiinflammatory effect. Glycine is the most simple aminoacid, but it is also an agonist of the glycine receptors (GlyR) that, when activated, cause that cells such as Kupffer cells, alveolar macrophages and neutrophils decrease their sensitivity to proinflammatory agents. Orally administered glycine has been used for some illnesses, and it has been noticed that it is well tolerated. Considering that children with CF have an intense inflammatory process in the airways, here we propose to use glycine as antiinflammatory agent.

Problem statement. Can a glycine oral supplement decrease the airway inflammation in children with CF?

Hypothesis. Compared with placebo, a daily supplement of glycine administered for 8 weeks to children with CF produce a statistically significant decrease of bronchial inflammation, measured by the concentration of neutrophils and inflammatory substances in sputum and peripheral blood, as well as by respiratory symptoms and spirometry.

Main objective: To determine whether a daily supplement of 0.5 g/kg glycine for 8 weeks significantly decrease the concentration, including neutrophils, interleukin(IL)-1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and myeloperoxidase, in sputum and peripheral blood of children with CF.

Secondary Objectives:

  1. To determine if glycine can improve respiratory symptoms, including decreased amount and better fluidity of sputum.
  2. To determine if glycine can improve spirometric variables.

Study design. This will be a randomized, placebo controlled, blinded, two-arms, cross-over clinical trial. Patients will receive glycine or placebo during the initial 8 weeks (initial phase), and after a 2 weeks washout period, they will receive the alternate treatment during another 8 weeks (second phase).

Material and methods: Children with CF fulfilling the selection criteria will be studied if their parents accept their participation. They will be randomly assigned to one of two groups. The experimental group will receive glycine and the control group will receive placebo (sugar glass), both at doses of 0.5 g/kg divided in 3 doses per os dissolved in any liquid. At study entry and at weeks 4, 8, 10, 14 and 18 we will collect a 2 ml blood sample and a sputum sample, and the children will be submitted to spirometry. A daily symptom questionnaire will be filled by the parents.

Statistical analysis: Each variable will be compared between experimental and control groups using Student's t test (or Mann Whitney U test if lacking normal distribution). Sample size: There are no previous studies that allow us to calculate a sample size. For convenience, it is estimated that 30 children can be included.

Time to complete: 24 months.

  Eligibility

Ages Eligible for Study:   5 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children of either sex
  • Between 5 and 15 years of age
  • With CF diagnosed according to established criteria
  • Without changes in the CF treatment in the last 30 days
  • Without CF exacerbation in the last 30 days
  • Without acute respiratory infection (e.g., common cold) in the last 15 days
  • Informed consent letter signed by their parents or legal guardians

Exclusion Criteria:

  • Children with CF that had participated in a research protocol in the last 3 months
  • Presence of serious adverse effects attributable to glycine, in which case the result will be considered as therapeutic failure in the statistical analysis
  • Development of a CF exacerbation, in which case the available data so far collected will be included in the statistical analysis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01417481

Locations
Mexico
Hospital Infantil de México
Mexico DF, Mexico, 06720
Instituto Nacional de Enfermedades Respiratorias
Mexico DF, Mexico, 14080
Unidad de Investigación Médica en Enfermedades Respiratorias, Hospital de Pediatría, CMN SXXI, IMSS
Mexico DF, Mexico, 06720
Sponsors and Collaborators
Instituto Nacional de Enfermedades Respiratorias
Hospital Infantil de Mexico Federico Gomez
Instituto Mexicano del Seguro Social
Investigators
Principal Investigator: Mario H Vargas, MD, MSc Instituto Nacional de Enfermedades Respiratorias
  More Information

Publications:
Responsible Party: Mario H. Vargas, Senior Researcher, Instituto Nacional de Enfermedades Respiratorias
ClinicalTrials.gov Identifier: NCT01417481     History of Changes
Other Study ID Numbers: Glycine in CF
Study First Received: August 15, 2011
Results First Received: September 9, 2014
Last Updated: October 30, 2014
Health Authority: Mexico: Ministry of Health

Keywords provided by Instituto Nacional de Enfermedades Respiratorias:
cystic fibrosis
glycine
airway inflammation

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Glycine
Glycine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014