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Functional Neuroimaging of Alcoholism Vulnerability (PIT) (CTNA)

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ClinicalTrials.gov Identifier: NCT01585168
Recruitment Status : Completed
First Posted : April 25, 2012
Results First Posted : May 25, 2018
Last Update Posted : May 25, 2018
Sponsor:
Information provided by (Responsible Party):
Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Memantine
Drug: Placebo
Enrollment 71
Recruitment Details 82 participants were screened for eligibility and then were consented at the Olin Research Center. However, after consent and prior to group randomization, 11 participants were excluded from the study due to follow-up eligibility paperwork (i.e. psychiatric interview, family history review, etc.) for a total of 71 randomized.
Pre-assignment Details  
Arm/Group Title Family History Negative (FHN): Memantine, Then Placebo Family History Negative (FHN): Placebo, Then Memantine Family History Positive (FHP): Memantine, Then Placebo Family History Positive (FHP): Placebo, Then Memantine
Hide Arm/Group Description

Participants received 2-20mg tablets of Memantine on the morning of the first study visit, then received 2 matching placebo tablets on the morning of the second study visit. Visits were approximately 1 week to 1 month a part on average.

Family History Negative (FHN): People who have no affected first- or second-degree relatives.

Participants received 2 matching placebo tablets on the morning of the first study visit, then received 2-20mg tablets of Memantine on the morning of the second study visit. Visits were approximately 1 week to 1 month a part on average.

Family History Negative (FHN): People who have no affected first- or second-degree relatives.

Participants received 2-20mg tablets of Memantine on the morning of the first study visit, then received 2 matching placebo tablets on the morning of the second study visit. Visits were approximately 1 week to 1 month a part on average.

Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.

Participants received 2 matching placebo tablets on the morning of the first study visit, then received 2-20mg tablets of Memantine on the morning of the second study visit. Visits were approximately 1 week to 1 month a part on average.

Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.

Period Title: Overall Study
Started 18 18 16 19
Completed 15 17 15 18
Not Completed 3 1 1 1
Reason Not Completed
Lost to Follow-up             3             1             1             1
Arm/Group Title Family History Positive (FHP) Family History Negative (FHN) Total
Hide Arm/Group Description People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism. People who have no affected first- or second-degree relatives. Total of all reporting groups
Overall Number of Baseline Participants 35 36 71
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 36 participants 71 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
35
 100.0%
36
 100.0%
71
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 33 participants 32 participants 65 participants
24.70
(18 to 34)
22.09
(19 to 27)
23.42
(18 to 34)
[1]
Measure Analysis Population Description: The number of participants analyzed is different from the overall baseline participants because a total of 6 participants (2 FHP, 4 FHN) did not complete both of the interventions (memantine, placebo) due to lost to follow-up.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 32 participants 65 participants
Female
28
  84.8%
20
  62.5%
48
  73.8%
Male
5
  15.2%
12
  37.5%
17
  26.2%
[1]
Measure Analysis Population Description: The number of participants analyzed is different from the overall baseline participants because a total of 6 participants (2 FHP, 4 FHN) did not complete both of the interventions (memantine, placebo) due to lost to follow-up.
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 33 participants 32 participants 65 participants
33 32 65
[1]
Measure Analysis Population Description: The number of participants analyzed is different from the overall baseline participants because a total of 6 participants (2 FHP, 4 FHN) did not complete both of the interventions (memantine, placebo) due to lost to follow-up.
1.Primary Outcome
Title Change in Blood Oxygenation Level Dependent (BOLD) Activation in the Amygdala During "Win" Monetary Incentive Delay (MID) Task Between Placebo and Study Medication
Hide Description All participants completed the fMRI Monetary Incentive Delay task on each study day. During the task, participants needed to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. Participant’s BOLD activation response (A measurement of oxygen level that is released to neurons since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen to perform the tasks.) was measured while they performed the task in MRI scanner.
Time Frame 4 hours post intervention on each study day, separated by 1 week to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects analyzed differs from the overall number of subjects because analyses for this measure occurred about 48 months into recruitment.
Arm/Group Title FHN - Memantine FHN - Placebo FHP - Memantine FHP - Placebo
Hide Arm/Group Description:
Family History Negative (FHN): People who have no affected first- or second-degree relatives.
Family History Negative (FHN): People who have no affected first- or second-degree relatives.
Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.
Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.
Overall Number of Participants Analyzed 27 27 12 12
Mean (Standard Deviation)
Unit of Measure: mean of voxel wise BOLD response
-0.6994  (3.8049) 1.7115  (3.9355) 0.3683  (3.9475) 4.0298  (5.6935)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FHN - Memantine, FHN - Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments P value was adjusted for multiple comparisons using FWE (family wise error) correction.
Method t-test, 2 sided
Comments A Paired t-test was performed to explore the difference between two groups.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.4109
Estimation Comments FHN was found to have lower mean BOLD activation while given drug compared to placebo in amygdala.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FHP - Memantine, FHP - Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 3.6615
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change in Blood Oxygenation Level Dependent (BOLD) Activation in Anterior Cingulate Cortex During "Loss" Condition of Monetary Incentive Delay (MID) Task Between Placebo and Study Medication
Hide Description All participants completed the fMRI Monetary Incentive Delay task on each study day. During the task, participants needed to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. Participant’s BOLD activation response (A measurement of oxygen level that is released to neurons since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen to perform the tasks.) was measured while they performed the task in MRI scanner.
Time Frame 4 hours post intervention on each study day, separated by 1 week to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects analyzed differs from the overall number of subjects because analyses for this measure occurred about 48 months into recruitment.
Arm/Group Title FHN - Memantine FHN - Placebo FHP - Memantine FHP - Placebo
Hide Arm/Group Description:
Family History Negative (FHN): People who have no affected first- or second-degree relatives.
Family History Negative (FHN): People who have no affected first- or second-degree relatives.
Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.
Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.
Overall Number of Participants Analyzed 27 27 12 12
Mean (Standard Deviation)
Unit of Measure: mean of voxel wise BOLD response
-0.5980  (2.9465) 1.2368  (2.8177) .7498  (3.1314) 3.4762  (2.3169)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FHP - Memantine, FHP - Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments P value was adjusted for multiple comparisons using FWE (family wise error) correction.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.7264
Estimation Comments FHP was found to have lower mean BOLD activation while given drug compared to placebo in anterior cingulate cortex.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FHN - Memantine, FHN - Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 1.8348
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Impulsive Behavior as Measured on the Balloon Analog Risk Task (BART) Computerized Task Between Placebo and Study Medication
Hide Description All participants completed the BART task approximately 3 hours post drug administration on both study visits. Study days were approximately 1 week to 1 month a part. BART is a computer decision-making task that measures risk taking. Participants are presented with a series of “balloons.” The object is to earn as much money as possible by pumping the balloon without popping it. The point of explosion varies from trial to trial and costs participants the money they have earned in that trial.
Time Frame 3 hours post intervention on each study day, separated by 1 week to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a family history of alcoholism (family history positive) and without a history of alcoholism (family history negative) who completed BART task.
Arm/Group Title FHN - Memantine FHN - Placebo FHP - Memantine FHP - Placebo
Hide Arm/Group Description:
Family History Negative (FHN): People who have no affected first- or second-degree relatives.
Family History Negative (FHN): People who have no affected first- or second-degree relatives.
Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.
Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.
Overall Number of Participants Analyzed 18 19 19 26
Mean (Standard Deviation)
Unit of Measure: total pumps
-0.12839  (1.001) -0.04331  (1.033) 0.2727  (0.910) -0.0789  (1.022)
4.Secondary Outcome
Title Change in Impulsive Behavior as Measured on the Experimental Discounting Delay (EDT) Computerized Task Between Placebo and Study Medication
Hide Description All participants completed the EDT task approximately 3 hours post drug administration on both study visits. Study days were approximately 1 week to 1 month a part. EDT is a delay-discounting task that exposes participants to choice consequences during test administration. The EDT involves multiple blocks of choices, one for each delay. Choices are made between a standard amount that is delivered immediately and is certain and a probable amount that is delayed and uncertain.
Time Frame 3 hours post intervention on each study day, separated by 1 week to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title FHN - Memantine FHN - Placebo FHP - Memantine FHP - Placebo
Hide Arm/Group Description:
Family History Negative (FHN): People who have no affected first- or second-degree relatives.
Family History Negative (FHN): People who have no affected first- or second-degree relatives.
Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.
Family History Positive (FHP): People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism.
Overall Number of Participants Analyzed 32 32 33 33
Mean (Standard Deviation)
Unit of Measure: responses
# of times "delayed" pressed in Delay Condition 13.58831  (6.838454) 14.13  (7.414) 15.41029  (8.256729) 13.64  (7.504)
# of times "immediate" pressed in Delay Condition 10.85871  (6.972910) 11.84  (7.133) 10.34057  (5.995089) 10.22  (5.873)
# of times "delayed" pressed in Immediate Cond. 11.44094  (3.890267) 11.94  (4.096) 11.77072  (4.882568) 11.50  (4.159)
# of times "immediate" pressed in Immediate Cond. 18.57818  (12.316437) 17.74  (10.847) 14.82459  (9.884165) 14.39  (10.431)
Time Frame AE data were collected over the duration of the study (4 years).
Adverse Event Reporting Description All AE information that were collected were expected side effects of the study medication.
 
Arm/Group Title Family History Positive (FHP) Family History Negative (FHN)
Hide Arm/Group Description People who have a biological father with alcoholism and at least one other first- or second-degree relative with alcoholism. People who have no affected first- or second-degree relatives.
All-Cause Mortality
Family History Positive (FHP) Family History Negative (FHN)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)      0/36 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Family History Positive (FHP) Family History Negative (FHN)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/35 (0.00%)      0/36 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Family History Positive (FHP) Family History Negative (FHN)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/35 (68.57%)      26/36 (72.22%)    
General disorders     
Dizziness   14/35 (40.00%)  14 12/36 (33.33%)  12
Lightheaded   19/35 (54.29%)  19 17/36 (47.22%)  17
"Drunk" or "Tipsy"  [1]  5/35 (14.29%)  5 2/36 (5.56%)  2
Nausea   2/35 (5.71%)  2 2/36 (5.56%)  2
Vomit   0/35 (0.00%)  0 1/36 (2.78%)  1
Indicates events were collected by systematic assessment
[1]
Study intervention did not involve use of alcohol, however one common side effect of the study medication includes feeling "drunk."
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Godfrey Pearlson
Organization: Yale University
Phone: (860) 545-7757
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01585168     History of Changes
Other Study ID Numbers: 1106008650
First Submitted: April 23, 2012
First Posted: April 25, 2012
Results First Submitted: November 3, 2017
Results First Posted: May 25, 2018
Last Update Posted: May 25, 2018