Minocycline for Alcohol Use Disorder
Primary Purpose
Alcohol Use Disorder, Inflammation, Neurocognitive Dysfunction
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Minocycline
Sugar pill
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol Use Disorder focused on measuring Minocycline
Eligibility Criteria
Inclusion Criteria:
- Ages 25 - 45
- Meet DSM-5 diagnostic criteria for an AUD [n.b., only participants with moderate or severe AUD will be enrolled]
- Drink ≥ 48 standard drinks in a 30-day period before enrollment
Exclusion Criteria:
- Currently in treatment for AUD, a history of treatment in the 30 days before enrollment, or currently treatment seeking
- Current (last 12 months) DSM-V diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine
- Lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder
- Positive urine screen for narcotics, amphetamines, or sedative hypnotics
- Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised
- Pregnancy, nursing, or refusal to use reliable method of birth control (if female)
- A medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes)
- AST, ALT, or GGT ≥ 3 times upper normal limit
- Attempted suicide in the past 3 years and/or serious suicidal intention or plan within the past year
- Currently on prescription medication that contraindicates use of MINO
- Any other circumstances that, in the opinion of the investigators, compromises participant safety.
- Claustrophobia
- Participating in any other research study involving exposure to ionizing radiation in the past year will be excluded if the total cumulative exposure from the past research studies and the current research study would exceed the limits set by the FDA in 21 CFR 361.1. Specifically, the total cumulated dose to the whole body, active blood-forming organs, lens of the eye, and gonads must remain below 5 rems, and the cumulated dose to all other organs must remain below 15 rems. Potential participants who have had exposure to ionizing radiation in the past year will not be allowed to participate if we are unable to obtain proper documentation quantifying the amount of past exposure.
- Presence of a metal device in the body (e.g., pacemaker, infusion pump, aneurysm clip, metal prosthesis or plate): Those devices could either interfere with the acquisition of the MRI scan of the brain or for whom the MRI scan would pose a potential risk. If participants have a non-removable device in their body, they must acquire and show a document exhibiting the device is MRI-compatible.
- low affinity rs6971 genotype
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Minocycline
Sugar Pill
Arm Description
200 mg/day
Matched placebo
Outcomes
Primary Outcome Measures
Microglial Activation
Level of [11C]DAA1106 binding during PET imaging
Cue-Induced Alcohol Craving
Alcohol Urge Questionnaire (AUQ)
Alcohol consumption
Total drinks consumed
Verbal Learning and Memory
Hopkins Verbal Learning Test
Set-Shifting
Wisconsin Card Sorting Test
Response Inhibition
Stop Signal Task
Manipulative Dexterity
Grooved Pegboard Test
Executive Function
Digit Symbol Substitution Test
Memory
Digit Span
Vocabulary
WAIS Vocabulary
Executive Function
Rey Complex Figure Copy
Secondary Outcome Measures
Peripheral Proinflammatory Marker levels
Serum level of cytokines and innate immune receptors
Alcohol Use Disorder Severity
Symptom count from the alcohol module for the Structured Clinical Interview for DSM-5
Full Information
NCT ID
NCT03244592
First Posted
July 28, 2017
Last Updated
January 22, 2019
Sponsor
University of California, Los Angeles
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1. Study Identification
Unique Protocol Identification Number
NCT03244592
Brief Title
Minocycline for Alcohol Use Disorder
Official Title
Development of Minocycline as a Neuroimmune Therapy for Alcohol Use Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Withdrawn
Why Stopped
Investigator left institution prior to enrollment of study participants
Study Start Date
January 15, 2018 (Anticipated)
Primary Completion Date
March 1, 2018 (Actual)
Study Completion Date
March 1, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Los Angeles
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this proposal is to advance medication development for alcohol use disorder by examining the efficacy and mechanisms of action of minocycline, a neuroimmune modulator, as a potential treatment. This study has important clinical implications, as the available treatments for alcohol use disorder are only modestly effective and testing novel medications is a high research priority.
Detailed Description
The research objective of this project is to advance medication development for AUD by conducting a randomized, double blind, placebo-controlled, neuroimaging study to examine the effects of minocycline on neuroinflammation, alcohol cue reactivity, neurocognitive performance, and alcohol use. In the proposed study, non-treatment seeking individuals with a current DSM-5 AUD diagnosis (N = 32) will be randomized to receive either 200 mg of minocycline per day or placebo for 28 days and complete two laboratory sessions. The first laboratory session will be performed immediately before commencing the medication regimen (day 0) and the second will be completed after taking the medication daily for 28 days. Within each laboratory session, participants will complete a cue reactivity paradigm, neurocognitive performance tasks, and a positron emission tomography (PET) imaging session. Neuroinflammation will be assessed by using PET imaging with the radiotracer N-(2,5-dimethoxy-benzyl)-N-(5-fluoro-2-phenoxyphenyl) acetamide, labeled with carbon-11 ([11C]-DAA1106), which binds to the mitochondrial translocator protein, a marker of activated microglia in brain. Additionally, blood samples will be drawn on days 0, 7, 14, 21, and 28 to measure circulating levels of proinflammatory markers and alcohol use over the four weeks of treatment will also be measured.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder, Inflammation, Neurocognitive Dysfunction, Craving, Alcohol Drinking
Keywords
Minocycline
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Double Blind
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Minocycline
Arm Type
Active Comparator
Arm Description
200 mg/day
Arm Title
Sugar Pill
Arm Type
Placebo Comparator
Arm Description
Matched placebo
Intervention Type
Drug
Intervention Name(s)
Minocycline
Intervention Description
200 mg/day
Intervention Type
Drug
Intervention Name(s)
Sugar pill
Other Intervention Name(s)
Placebo
Intervention Description
Matched placebo
Primary Outcome Measure Information:
Title
Microglial Activation
Description
Level of [11C]DAA1106 binding during PET imaging
Time Frame
Change from baseline after 28 days of medication dosing
Title
Cue-Induced Alcohol Craving
Description
Alcohol Urge Questionnaire (AUQ)
Time Frame
Change from baseline after 28 days of medication dosing
Title
Alcohol consumption
Description
Total drinks consumed
Time Frame
Day 28 of medication dosing period
Title
Verbal Learning and Memory
Description
Hopkins Verbal Learning Test
Time Frame
Change from baseline after 28 days of medication dosing
Title
Set-Shifting
Description
Wisconsin Card Sorting Test
Time Frame
Change from baseline after 28 days of medication dosing
Title
Response Inhibition
Description
Stop Signal Task
Time Frame
Change from baseline after 28 days of medication dosing
Title
Manipulative Dexterity
Description
Grooved Pegboard Test
Time Frame
Change from baseline after 28 days of medication dosing
Title
Executive Function
Description
Digit Symbol Substitution Test
Time Frame
Change from baseline after 28 days of medication dosing
Title
Memory
Description
Digit Span
Time Frame
Change from baseline after 28 days of medication dosing
Title
Vocabulary
Description
WAIS Vocabulary
Time Frame
Change from baseline after 28 days of medication dosing
Title
Executive Function
Description
Rey Complex Figure Copy
Time Frame
Change from baseline after 28 days of medication dosing
Secondary Outcome Measure Information:
Title
Peripheral Proinflammatory Marker levels
Description
Serum level of cytokines and innate immune receptors
Time Frame
At baseline (day zero) and after 7, 14, and 21 and 28 days of medication dosing
Title
Alcohol Use Disorder Severity
Description
Symptom count from the alcohol module for the Structured Clinical Interview for DSM-5
Time Frame
At baseline (day zero) and after 28 days of medication dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ages 25 - 45
Meet DSM-5 diagnostic criteria for an AUD [n.b., only participants with moderate or severe AUD will be enrolled]
Drink ≥ 48 standard drinks in a 30-day period before enrollment
Exclusion Criteria:
Currently in treatment for AUD, a history of treatment in the 30 days before enrollment, or currently treatment seeking
Current (last 12 months) DSM-V diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine
Lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder
Positive urine screen for narcotics, amphetamines, or sedative hypnotics
Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised
Pregnancy, nursing, or refusal to use reliable method of birth control (if female)
A medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes)
AST, ALT, or GGT ≥ 3 times upper normal limit
Attempted suicide in the past 3 years and/or serious suicidal intention or plan within the past year
Currently on prescription medication that contraindicates use of MINO
Any other circumstances that, in the opinion of the investigators, compromises participant safety.
Claustrophobia
Participating in any other research study involving exposure to ionizing radiation in the past year will be excluded if the total cumulative exposure from the past research studies and the current research study would exceed the limits set by the FDA in 21 CFR 361.1. Specifically, the total cumulated dose to the whole body, active blood-forming organs, lens of the eye, and gonads must remain below 5 rems, and the cumulated dose to all other organs must remain below 15 rems. Potential participants who have had exposure to ionizing radiation in the past year will not be allowed to participate if we are unable to obtain proper documentation quantifying the amount of past exposure.
Presence of a metal device in the body (e.g., pacemaker, infusion pump, aneurysm clip, metal prosthesis or plate): Those devices could either interfere with the acquisition of the MRI scan of the brain or for whom the MRI scan would pose a potential risk. If participants have a non-removable device in their body, they must acquire and show a document exhibiting the device is MRI-compatible.
low affinity rs6971 genotype
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Roche, PhD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Minocycline for Alcohol Use Disorder
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