Trial Outcomes & Findings for Effect of Glycine in Cystic Fibrosis (NCT NCT01417481)
NCT ID: NCT01417481
Last Updated: 2014-11-05
Results Overview
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.
TERMINATED
PHASE2
13 participants
8 weeks
2014-11-05
Participant Flow
Patients attending the Hospital Infantil de México and the Instituto Mexicano del Seguro Social (both in Mexico city) were recruited from March 7, 2012 to October 31, 2012. The two arms of the study were: 1) Glycine, then placebo, and 2) Placebo, then glycine.
Participant milestones
| Measure |
Glycine, Then Placebo
First intervention (8 weeks) with Glycine (0.5 g/kg/day divided in three doses).
Washout period of 2 weeks. Second intervention (8 weeks) with Placebo (sugar glass, 0.5 g/kg/day divided in three doses).
|
Placebo, Then Glycine
First intervention (8 weeks) with Placebo (sugar glass, 0.5 g/kg/day divided in three doses).
Washout period of 2 weeks. Second intervention (8 weeks) with Glycine (0.5 g/kg/day divided in three doses).
|
|---|---|---|
|
First Intervention (8 Weeks)
STARTED
|
8
|
7
|
|
First Intervention (8 Weeks)
COMPLETED
|
8
|
5
|
|
First Intervention (8 Weeks)
NOT COMPLETED
|
0
|
2
|
|
Washout (2 Weeks)
STARTED
|
8
|
5
|
|
Washout (2 Weeks)
COMPLETED
|
8
|
5
|
|
Washout (2 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Second Period (8 Weeks)
STARTED
|
8
|
5
|
|
Second Period (8 Weeks)
COMPLETED
|
8
|
5
|
|
Second Period (8 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Glycine, Then Placebo
First intervention (8 weeks) with Glycine (0.5 g/kg/day divided in three doses).
Washout period of 2 weeks. Second intervention (8 weeks) with Placebo (sugar glass, 0.5 g/kg/day divided in three doses).
|
Placebo, Then Glycine
First intervention (8 weeks) with Placebo (sugar glass, 0.5 g/kg/day divided in three doses).
Washout period of 2 weeks. Second intervention (8 weeks) with Glycine (0.5 g/kg/day divided in three doses).
|
|---|---|---|
|
First Intervention (8 Weeks)
Withdrawal by Subject
|
0
|
2
|
Baseline Characteristics
Effect of Glycine in Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Glycine, Then Placebo
n=8 Participants
First intervention (8 weeks) with Glycine (0.5 g/kg/day divided in three doses).
Washout period of 2 weeks. Second intervention (8 weeks) with Placebo (sugar glass, 0.5 g/kg/day divided in three doses).
|
Placebo, Then Glycine
n=7 Participants
First intervention (8 weeks) with Placebo (sugar glass, 0.5 g/kg/day divided in three doses).
Washout period of 2 weeks. Second intervention (8 weeks) with Glycine (0.5 g/kg/day divided in three doses).
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
14.39 years
STANDARD_DEVIATION 5.82 • n=5 Participants
|
11.00 years
STANDARD_DEVIATION 4.01 • n=7 Participants
|
12.81 years
STANDARD_DEVIATION 5.19 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
8 participants
n=5 Participants
|
7 participants
n=7 Participants
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: From the 13 patients who initiated the study, some parents did not give consent for blood sampling, and some children refused the venous puncture at some visits. Thus, only a non-paired population of 9 children per group could be analyzed.
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.
Outcome measures
| Measure |
Glycine
n=9 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=9 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
MCP-1
|
-0.0836 log (percent change)
Standard Error 0.1041
|
0.0472 log (percent change)
Standard Error 0.0894
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
MIP-1beta
|
0.0330 log (percent change)
Standard Error 0.1426
|
-0.0608 log (percent change)
Standard Error 0.0963
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
Myeloperoxidase
|
-0.4361 log (percent change)
Standard Error 0.2184
|
-0.2906 log (percent change)
Standard Error 0.2877
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
IL-1
|
-0.1635 log (percent change)
Standard Error 0.1467
|
-0.0352 log (percent change)
Standard Error 0.1294
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
IL-4
|
0.2964 log (percent change)
Standard Error 0.1420
|
0.1470 log (percent change)
Standard Error 0.2223
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
IL-6
|
0.0085 log (percent change)
Standard Error 0.2064
|
0.2255 log (percent change)
Standard Error 0.1865
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
IL-7
|
0.0356 log (percent change)
Standard Error 0.0613
|
0.0819 log (percent change)
Standard Error 0.0986
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
IL-8
|
-0.1466 log (percent change)
Standard Error 0.2981
|
-0.2364 log (percent change)
Standard Error 0.1761
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
IL-12
|
0.3203 log (percent change)
Standard Error 0.1449
|
0.2603 log (percent change)
Standard Error 0.2117
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
IL-13
|
-0.0561 log (percent change)
Standard Error 0.1684
|
0.1953 log (percent change)
Standard Error 0.1849
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
G-CSF
|
-0.0776 log (percent change)
Standard Error 0.1554
|
0.2272 log (percent change)
Standard Error 0.1983
|
|
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
IFN-gamma
|
0.3272 log (percent change)
Standard Error 0.1761
|
0.3639 log (percent change)
Standard Error 0.2505
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: From the 13 patients who initiated the study, some children at some visits could not give an appropriate sputum sample. Thus, only a non-paired population of 9 (glycine group) and 11 (placebo group) children could be analyzed.
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.
Outcome measures
| Measure |
Glycine
n=9 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=11 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
Myeloperoxidase
|
0.1294 log (percent change)
Standard Error 0.2204
|
0.0669 log (percent change)
Standard Error 0.1725
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-1
|
-0.0918 log (percent change)
Standard Error 0.1552
|
-0.0102 log (percent change)
Standard Error 0.1329
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-2
|
0.0233 log (percent change)
Standard Error 0.0828
|
-0.0274 log (percent change)
Standard Error 0.1243
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-4
|
-0.0161 log (percent change)
Standard Error 0.0482
|
0.0522 log (percent change)
Standard Error 0.0671
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-5
|
0.2498 log (percent change)
Standard Error 0.1855
|
0.1304 log (percent change)
Standard Error 0.1864
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-7
|
0.0611 log (percent change)
Standard Error 0.0852
|
0.1387 log (percent change)
Standard Error 0.1028
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-8
|
-0.0824 log (percent change)
Standard Error 0.2311
|
0.0542 log (percent change)
Standard Error 0.0934
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-10
|
0.0549 log (percent change)
Standard Error 0.0847
|
0.0074 log (percent change)
Standard Error 0.0849
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-12
|
0.1675 log (percent change)
Standard Error 0.1443
|
0.0677 log (percent change)
Standard Error 0.1250
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-13
|
0.1630 log (percent change)
Standard Error 0.1379
|
0.0953 log (percent change)
Standard Error 0.1049
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IL-17
|
0.0680 log (percent change)
Standard Error 0.0411
|
0.1140 log (percent change)
Standard Error 0.0823
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
IFN-gamma
|
0.0248 log (percent change)
Standard Error 0.0652
|
0.0649 log (percent change)
Standard Error 0.0730
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
MCP-1
|
0.0042 log (percent change)
Standard Error 0.0694
|
0.2608 log (percent change)
Standard Error 0.2025
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
MIP-1beta
|
-0.0303 log (percent change)
Standard Error 0.1234
|
0.0977 log (percent change)
Standard Error 0.1207
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
TNF-alpha
|
0.0412 log (percent change)
Standard Error 0.1091
|
0.1568 log (percent change)
Standard Error 0.1393
|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
GM-CSF
|
-0.0538 log (percent change)
Standard Error 0.0338
|
-0.0822 log (percent change)
Standard Error 0.0468
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: From the 13 patients who initiated the study, some parents did not give consent for blood sampling, and some children refused the venous puncture at some visits. Thus, only a non-paired population of 9 children per group could be analyzed.
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.
Outcome measures
| Measure |
Glycine
n=9 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=9 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Serum Concentration of Inflammatory Biomarkers (TNF-alpha)
|
-0.3908 log (percent change)
Standard Error 0.2744
|
0.2035 log (percent change)
Standard Error 0.2384
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: From the 13 patients who initiated the study, some children did not expectorate at some visits. Thus, only a non-paired population of 9 children under glycine and 11 under placebo could be analyzed.
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.
Outcome measures
| Measure |
Glycine
n=9 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=11 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (IL-6)
|
-0.00007 log (percent change)
Standard Error 0.0677
|
0.1739 log (percent change)
Standard Error 0.0838
|
PRIMARY outcome
Timeframe: 8 weeksTo 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.
Outcome measures
| Measure |
Glycine
n=9 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=11 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Sputum Concentration of Inflammatory Biomarkers (G-CSF)
|
-0.0819 log (percent change)
Standard Error 0.0790
|
0.1668 log (percent change)
Standard Error 0.1022
|
SECONDARY outcome
Timeframe: 8 weeksTo 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.
Outcome measures
| Measure |
Glycine
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Cough questionnaire score
|
81.1 Percentage of baseline
Standard Error 12.6
|
89.1 Percentage of baseline
Standard Error 4.9
|
|
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Appetite questionnaire score
|
89.1 Percentage of baseline
Standard Error 11.0
|
132.1 Percentage of baseline
Standard Error 25.4
|
|
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Energy questionnaire score
|
84.6 Percentage of baseline
Standard Error 7.4
|
111.5 Percentage of baseline
Standard Error 16.2
|
|
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Body weight
|
101.6 Percentage of baseline
Standard Error 1.1
|
103.6 Percentage of baseline
Standard Error 1.0
|
|
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Height
|
100.5 Percentage of baseline
Standard Error 0.2
|
100.5 Percentage of baseline
Standard Error 0.2
|
|
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Heart rate
|
103.5 Percentage of baseline
Standard Error 6.0
|
98.1 Percentage of baseline
Standard Error 3.0
|
|
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Respiratory rate
|
94.8 Percentage of baseline
Standard Error 5.5
|
109.0 Percentage of baseline
Standard Error 6.4
|
|
Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)
Temperature
|
100.0 Percentage of baseline
Standard Error 0.3
|
100.1 Percentage of baseline
Standard Error 0.5
|
SECONDARY outcome
Timeframe: 8 weeksTo 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.
Outcome measures
| Measure |
Glycine
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Score for Sputum Production, Dyspnea and Global Symptoms
Dyspnea questionnaire score
|
75.6 Percentage of baseline
Standard Error 7.5
|
103.8 Percentage of baseline
Standard Error 10.7
|
|
Changes in Score for Sputum Production, Dyspnea and Global Symptoms
Sputum questionnaire score
|
82.0 Percentage of baseline
Standard Error 7.0
|
102.6 Percentage of baseline
Standard Error 10.1
|
|
Changes in Score for Sputum Production, Dyspnea and Global Symptoms
Total questionnaire score
|
77.7 Percentage of baseline
Standard Error 5.2
|
98.7 Percentage of baseline
Standard Error 8.4
|
SECONDARY outcome
Timeframe: 8 weeksTo correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value \[beginning of the glycine or placebo period, respectively\]).
Outcome measures
| Measure |
Glycine
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Pulse Oximetry, FEV1/FVC, and FEF50.
Peripheral oxygen saturation (SpO2)
|
105.2 Percentage of baseline
Standard Error 2.5
|
98.9 Percentage of baseline
Standard Error 1.4
|
|
Changes in Pulse Oximetry, FEV1/FVC, and FEF50.
FEV1/FVC
|
105.2 Percentage of baseline
Standard Error 2.9
|
94.9 Percentage of baseline
Standard Error 4.2
|
|
Changes in Pulse Oximetry, FEV1/FVC, and FEF50.
Forced expiratory flow at 50%FVC (FEF50)
|
115.5 Percentage of baseline
Standard Error 10.4
|
93.1 Percentage of baseline
Standard Error 7.8
|
SECONDARY outcome
Timeframe: 8 weeksTo correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value \[beginning of the glycine or placebo period, respectively\]).
Outcome measures
| Measure |
Glycine
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in FEV1, FEF25, and FEFmax
Forced expiratory volume at first second (FEV1)
|
109.7 Percentage of baseline
Standard Error 6.4
|
91.4 Percentage of baseline
Standard Error 4.1
|
|
Changes in FEV1, FEF25, and FEFmax
Forced expiratory flow at 25%FVC (FEF25)
|
133.9 Percentage of baseline
Standard Error 13.6
|
83.3 Percentage of baseline
Standard Error 7.7
|
|
Changes in FEV1, FEF25, and FEFmax
Maximal forced expiratory flow (FEFmax, PEFR)
|
115.3 Percentage of baseline
Standard Error 6.1
|
91.2 Percentage of baseline
Standard Error 4.6
|
SECONDARY outcome
Timeframe: 8 weeksTo correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value \[beginning of the glycine or placebo period, respectively\]).
Outcome measures
| Measure |
Glycine
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg glycine dissolved in water during 8 weeks.
|
Placebo
n=13 Participants
All study participants receiving a daily oral supplement of 0.5 g/kg placebo (sugar glass) dissolved in water during 8 weeks.
|
|---|---|---|
|
Changes in Other Spirometric Variables
Forced vital capacity (FVC)
|
104.1 Percentage of baseline
Standard Error 4.1
|
100.6 Percentage of baseline
Standard Error 9.8
|
|
Changes in Other Spirometric Variables
Forced expiratory flow at 75%FVC (FEF75)
|
111.8 Percentage of baseline
Standard Error 11.7
|
108.9 Percentage of baseline
Standard Error 15.8
|
Adverse Events
Glycine
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Mario H. Vargas
Instituto Nacional de Enfermedades Respiratorias
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place