N/A
Completed N=57
Glycine and Oral D-Cycloserine in Alcoholic Patients and Healthy Subjects
Source: ClinicalTrials.gov NCT00635102 ↗Enrolled (actual)
57
Serious AEs
0.0%
Results posted
Dec 2016
Primary outcomePrimary: Visual Analog Scales of Similarity to Alcohol - Baseline — 0.18; 0.05; 0.25; 0.04 units on a scale
Summary
Question #1: Will glycine ameliorate cognitive deficits? Hypothesis #1: Based on positive findings conducted with glycine and milacemide, a glycine prodrug, in schizophrenia and dementia, we expect that glycine will ameliorate cognitive deficits.
Question #2: Will alcoholic patients show enhanced endocrinal effects to glycine? Hypothesis #2: Based on the dose-related effects of glycine in healthy subjects, we expect that glycine will increase the endocrinal response to glycine in alcoholic patients with, supposedly, dysregulated NMDA receptor function.
Question #3: Will D-cycloserine have ethanol-like effects? Hypothesis #3: If inhibition of NMDA receptor function is fundamental to the subjective effects of ethanol, then the NMDA antagonist properties of D-cycloserine should be recognized as ethanol-like (relative to placebo) in recently detoxified alcoholics and healthy subjects.
Question #4: Will D-cycloserine reverse cognitive benefits of glycine? Hypothesis 4: Based on the dose related NMDA antagonist activity of D-cycloserine, we expect that D-cycloserine will compete with the agonist activity of glycine and therefore it will reverse the cognitive benefits of glycine.
Question #5: Will D-cycloserine inhibit endocrinal effects of glycine? Hypothesis #5: If the agonist activity of glycine is necessary to determine endocrine response, then the dose-related NMDA antagonist properties of D-cycloserine should block these effects.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Visual Analog Scales of Similarity to Alcohol - Baseline |
0.18; 0.05; 0.25; 0.04; 0.10; 0.04 | — |
| PRIMARY Visual Analog Scales of Similarity to Alcohol 60 Minutes Prior to Glycine Infusion |
0.77; 1.41; 0.65; 0.67; 0.48; 1.17 | — |
| PRIMARY Visual Analog Scales of Similarity to Alcohol 30 Minutes |
0.57; 1.81; 0.60; 0.71; 1.05; 1.21 | — |
| PRIMARY Visual Analog Scales of Similarity to Alcohol 60 Minutes |
0.67; 1.81; 0.75; 0.70; 0.81; 1.46 | — |
| PRIMARY Visual Analog Scales of Similarity to Alcohol 120 Minutes |
0.43; 0.41; 0.3; 0.09; 0.57; 0.29 | — |
| SECONDARY Number of Drinks Felt Consumed at 60 Minutes Prior to Glycine Infusion |
0.50; 0.70; 0.30; 0.25; 0.24; 0.75 | — |
| SECONDARY Number of Drinks Felt Consumed at 30 Minutes |
0.38; 0.68; 0.20; 0.13; 0.38; 0.38 | — |
| SECONDARY Number of Drinks Felt Consumed at 60 Minutes |
0.05; 1.24; 0.5; 0.4; 0.86; 0.83 | — |
| SECONDARY Number of Drinks Felt Consumed at 120 Minutes |
0; 0.13; 0.1; 0.21; 0.05; 0 | — |
| SECONDARY Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - Baseline |
3.41; 1.91; 3.3; 2.75; 3.57; 1.83 | — |
| SECONDARY Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation 60 Minutes Prior to Glycine Infusion |
6.23; 7.39; 6.6; 3.79; 7.24; 6.25 | — |
| SECONDARY Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 30 Minutes |
7.14; 10.05; 5.8; 5.87; 5.2; 7.04 | — |
| SECONDARY Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 60 Minutes |
5.29; 9.64; 5.65; 5.83; 8.48; 8.54 | — |
| SECONDARY Biphasic Alcohol Effects Scale (BAES) Subscale Sedation - 120 Minutes |
3.57; 4.13; 4.35; 1.67; 4; 3.04 | — |
| SECONDARY Visual Analog Scales (VAS) - Baseline |
0.32; 0.22; 0.5; 0.22; 0.76; 0.25 | — |
| SECONDARY Visual Analog Scales (VAS) - 60 Minutes Prior to Glycine Infusion |
0.64; 0.82; 0.68; 0.33; 0.48; 0.96 | — |
| SECONDARY Visual Analog Scales (VAS) - 30 Minutes |
0.48; 1.05; 0.65; 0.30; 0.48; 0.79 | — |
| SECONDARY Visual Analog Scales (VAS) - 60 Minutes |
0.52; 0.91; 0.8; 0.22; 0.6; 0.71 | — |
| SECONDARY Visual Analog Scales (VAS) - 120 Minutes |
0.8; 0.35; 0.55; 0.21; 0.76; 0.29 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Desire to Drink- Baseline |
7.62; 3.04; 9.5; 2.5; 5; 1.67 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes Prior to Glycine Infusion |
7.27; 2.61; 8.5; 1.67; 6.67; 3.04 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Desire to Drink: - 30 Minutes |
9.05; 1.82; 9; 2.17; 8; 2.5 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 60 Minutes |
6.5; 1.82; 9; 2.17; 10.48; 1.67 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Desire to Drink - 120 Minutes |
6.19; 1.30; 8; 1.667; 9.05; 2.08 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Mood Improvement - Baseline |
6.67; 1.74; 10.5; 0.42; 6.82; 0.42 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes Prior to Glycine Infusion |
7.73; 0.87; 8; 0.83; 7.62; 1.30 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 30 Minutes |
11.43; 0.91; 8; 0.87; 10.5; 0.42 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 60 Minutes |
5.5; 0.46; 8.5; 0.87; 8.1; 0.83 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Mood Improvement - 120 Minutes |
6.19; 0.87; 7; 0.83; 8.57; 0.42 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Discomfort - Baseline |
8.1; 2.61; 12.5; 1.67; 7.73; 0.42 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes Prior to Glycine Infusion |
6.36; 1.30; 8.95; 1.25; 7.14; 0.44 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Discomfort - 30 Minutes |
12.38; 1.82; 8.95; 1.74; 9.5; 0.42 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Discomfort - 60 Minutes |
6.5; 1.36; 10.5; 1.74; 9.05; 0.42 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Discomfort - 120 Minutes |
8.57; 1.14; 9.5; 1.67; 9.05; 0.42 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - Baseline |
29.05; 93.48; 35.5; 94.58; 42.27; 99.17 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes Prior to Glycine Infusion |
30.46; 98.26; 40.5; 95; 36.67; 99.13 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 30 Minutes |
32.86; 99.1; 36; 98.70; 36.5; 99.17 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 60 Minutes |
34; 99.1; 39.5; 99.13; 25.71; 99.17 | — |
| SECONDARY Alcohol Craving Scale (ACS) Subscale: Reduced Control of Alcohol Use - 120 Minutes |
34.29; 98.26; 33.5; 99.17; 30.48; 99.17 | — |
| SECONDARY Continuous Performance Task (CPT) - Distractibility A-Prime - 30 Minutes |
0.93; 0.1; 0.97; 0.1; 0.90; 0.1 | — |
| SECONDARY Continuous Performance Task (CPT) - Vigilance - A-Prime Score 30 Minutes |
0.98; 0.1; 0.1; 0.1; 0.1; 0.1 | — |
| SECONDARY Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 1 |
5.29; 7.09; 6.05; 8.52; 5.48; 7.75 | — |
| SECONDARY Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 2 |
7.67; 10.09; 8.45; 11.09; 7.1; 10.5 | — |
| SECONDARY Hopkins Verbal Learning Task - Immediate Recall - 60 Minutes - Trial 3 |
8; 10.57; 9.2; 11.48; 8.48; 11.17 | — |
| SECONDARY Hopkins Verbal Learning Task - Delay Recall - 90 Minutes |
5.1; 9.7; 7.75; 10.87; 6.29; 10.21 | — |
Eligibility Criteria
Inclusion / Exclusion Criteria Alcoholic subjects:
- Male or female (post-menopausal, surgically sterile, or negative pregnancy test at screening and agreement to utilize an established birth control during the testing period) between the age of 21 and 70 yrs.
- Meet Diagnostic and Statistical Manual (DSM) IV criteria for alcohol dependence by structured clinical interview
- Meet von Knorring criteria for early onset (type II) alcoholism
- Without other DSM IV Axis I diagnoses by Structured Clinical Interview (SCID).
- Without lifetime history of other substance abuse diagnosis by SCID (excluding tobacco) and urine toxicology screen negative for drug of abuse.
- Medically and neurologically healthy on the basis of history, physical examination, sequential multiple analysis-computer (SMAC-20), complete blood count (CBC) w/diff. and EKG. In light of the proximity to alcohol dependence, liver function test (LFT) elevations of twice normal will be accepted into the study.
- Patients with stable medical problems may be included in the study if their medications have not been adjusted in the month prior to participation and if these medications lack prominent central nervous system (CNS) effects.
- Absence of alcohol within the past 15 days.
- Patients must be free of medications utilized to facilitate detoxification (lorazepam, oxazepam) for at least 3 days prior to initiating testing.
- Patients must have no history of alcoholic hallucinosis.
- Patients must not be in acute alcohol withdrawal as evidence by a score no more than 2 for each item of the Clinical Institute Withdrawal Assessment Scale
- Patients taking ethionamide or isoniazid will be not be allowed to participate in the study.
Inclusion / Exclusion Criteria Healthy subjects:
- Male or female (post-menopausal, surgically sterile, or negative pregnancy test at screening and agreement to utilize an established birth control during the testing period) between the age of 21 and 70 yrs.
- Absence of a lifetime substance abuse diagnosis by the non-patient version of the SCID.
- Medically and neurologically healthy on the basis of history, physical examination, SMAC-20, CBC w/diff. and EKG. In light of the proximity to alcohol dependence, LFT elevations of twice normal will be accepted into the study.
- Absence of alcohol within the past 14 days
- Healthy subjects will be matched to the patient group for age, sex and educational level.
Data sourced from ClinicalTrials.gov (NCT00635102). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.