Clinical trial NCT03244592: Minocycline for Alcohol Use Disorder
Official title: Development of Minocycline as a Neuroimmune Therapy for Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Alcohol Use Disorder
Inflammation
Neurocognitive Dysfunction
Craving
Alcohol Drinking
Keywords: Minocycline
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2017-08-09
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Ages 25 - 45
2. Meet DSM-5 diagnostic criteria for an AUD \[n.b., only participants with moderate or severe AUD will be enrolled\]
3. Drink ≥ 48 standard drinks in a 30-day period before enrollment

Exclusion Criteria:

1. Currently in treatment for AUD, a history of treatment in the 30 days before enrollment, or currently treatment seeking
2. Current (last 12 months) DSM-V diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine
3. Lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder
4. Positive urine screen for narcotics, amphetamines, or sedative hypnotics
5. Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised
6. Pregnancy, nursing, or refusal to use reliable method of birth control (if female)
7. A medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes)
8. AST, ALT, or GGT ≥ 3 times upper normal limit
9. Attempted suicide in the past 3 years and/or serious suicidal intention or plan within the past year
10. Currently on prescription medication that contraindicates use of MINO
11. Any other circumstances that, in the opinion of the investigators, compromises participant safety.
12. Claustrophobia
13. 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.
14. 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.
15. low affinity rs6971 genotype

Primary outcomes:
measure: Microglial Activation
timeFrame: Change from baseline after 28 days of medication dosing
measure: Cue-Induced Alcohol Craving
timeFrame: Change from baseline after 28 days of medication dosing
measure: Alcohol consumption
timeFrame: Day 28 of medication dosing period
measure: Verbal Learning and Memory
timeFrame: Change from baseline after 28 days of medication dosing
measure: Set-Shifting
timeFrame: Change from baseline after 28 days of medication dosing
measure: Response Inhibition
timeFrame: Change from baseline after 28 days of medication dosing
measure: Manipulative Dexterity
timeFrame: Change from baseline after 28 days of medication dosing
measure: Executive Function
timeFrame: Change from baseline after 28 days of medication dosing
measure: Memory
timeFrame: Change from baseline after 28 days of medication dosing
measure: Vocabulary
timeFrame: Change from baseline after 28 days of medication dosing
measure: Executive Function
timeFrame: Change from baseline after 28 days of medication dosing
Secondary outcomes:
measure: Peripheral Proinflammatory Marker levels
timeFrame: At baseline (day zero) and after 7, 14, and 21 and 28 days of medication dosing
measure: Alcohol Use Disorder Severity
timeFrame: At baseline (day zero) and after 28 days of medication dosing
Other outcomes:
Locations:
Study officials:
affiliation: University of California, Los Angeles
name: Daniel Roche, PhD
role: PRINCIPAL_INVESTIGATOR
References: