Effect of Glycine in Cystic Fibrosis

October 30, 2014 updated by: Mario H. Vargas, Instituto Nacional de Enfermedades Respiratorias

Evaluation of the Capability of a Glycine Oral Supplement for Diminishing Bronchial Inflammation in Children With Cystic Fibrosis

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • Mexico DF, Mexico, 14080
        • Instituto Nacional de Enfermedades Respiratorias
      • Mexico DF, Mexico, 06720
        • Hospital Infantil de Mexico
      • Mexico DF, Mexico, 06720
        • Unidad de Investigación Médica en Enfermedades Respiratorias, Hospital de Pediatría, CMN SXXI, IMSS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 13 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • sugar glass

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
Time Frame: 8 weeks
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.
8 weeks
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
Time Frame: 8 weeks
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.
8 weeks
Changes in Serum Concentration of Inflammatory Biomarkers (TNF-alpha)
Time Frame: 8 weeks
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.
8 weeks
Changes in Sputum Concentration of Inflammatory Biomarkers (IL-6)
Time Frame: 8 weeks
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.
8 weeks
Changes in Sputum Concentration of Inflammatory Biomarkers (G-CSF)
Time Frame: 8 weeks
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.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Time Frame: 8 weeks

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.
8 weeks
Changes in Score for Sputum Production, Dyspnea and Global Symptoms
Time Frame: 8 weeks

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.
8 weeks
Changes in Pulse Oximetry, FEV1/FVC, and FEF50.
Time Frame: 8 weeks
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]).
8 weeks
Changes in FEV1, FEF25, and FEFmax
Time Frame: 8 weeks
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]).
8 weeks
Changes in Other Spirometric Variables
Time Frame: 8 weeks
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]).
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Enfermedades Respiratorias

Collaborators

Instituto Mexicano del Seguro Social
Hospital Infantil de Mexico Federico Gomez

Investigators

  • Principal Investigator: Mario H Vargas, MD, MSc, Instituto Nacional de Enfermedades Respiratorias

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

August 15, 2011

First Submitted That Met QC Criteria

August 15, 2011

First Posted (Estimate)

August 16, 2011

Study Record Updates

Last Update Posted (Estimate)

November 5, 2014

Last Update Submitted That Met QC Criteria

October 30, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Glycine in CF

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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