Aripiprazole and Topiramate on Free-Choice Alcohol Use

NCT00884884 | Completed Phase 2

• 2 other identifiers: NIAAA-Swift-AA015753NIH Grant 5RO1AA015753-02
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The current study investigates the effects of two potential alcohol treatment medications on drinking in a laboratory setting. Aripiprazole (APZ), effects dopamine and serotonin receptors with fewer limiting side effects seen with other atypical antipsychotics. Topiramate (TPMT), an antiepileptic, affects glutamate and GABA-A receptors and shows promise in reducing heavy drinking. Few studies have used two medications with such a diverse combination of actions to examine a potential synergistic effect on reducing alcohol consumption. The primary aims are to:

1. 1.determine if APZ and TPMT are each more effective than placebo, and the combination of APZ and TPMT is more effective than either drug alone or placebo, in reducing alcohol use in non-treatment seeking alcohol dependent subjects in a laboratory based alcohol self-administration experiment (ASAE)
2. 2.examine a hypothesized dose-response for three doses of APZ (0, 7.5 mg/d and 15 mg/d) along with three doses of TPMT (0, 100mg/d and 200mg/d)
3. 3.examine the putative mechanisms of action of APZ, TPMT alone and together on craving, subjective stimulation, candidate gene influences and other behavioral effects associated with alcohol consumption
4. 4.establish the safety of giving APZ and TPMT together. Non-treatment seeking, alcohol dependent Participants (N=216) will be recruited from the community and randomly assigned to one of the 9 cells. Subjects drinking and safety is monitored over a 5-week titration to their target dose, leading to an in-laboratory alcohol self administration session, during which clinical and behavioral effects are assessed during access to alcohol. A 1 month follow-up assesses adverse events and drinking.

Conditions

Alcohol Dependence

Keywords

Alcohol dependence; alcohol abuse; topiramate; aripiprazole

Outcome Measures

Primary Outcomes (2)

• Number of alcoholic drinks consumed in a laboratory setting

  90 minutes

• Safety and tolerability of the medications singly and in combination, compared to placebo

  4 years

Secondary Outcomes (1)

• Drinks consumed during the medication titration period

  4 weeks

Study Arms (9)

Double Placebo

PLACEBO COMPARATOR

Placebo, Placebo

Drug: Double Placebo

Aripiprazole 15, Placebo

EXPERIMENTAL

15 mg Aripiprazole, Placebo

Drug: Aripiprazole 15, placebo

Aripiprazole 7.5, Placebo

EXPERIMENTAL

Aripiprazole 7.5 mg daily plus Placebo daily

Drug: Aripiprazole 7.5, Placebo

Topiramate 100mg, Placebo

EXPERIMENTAL

Topiramate 100 mg daily plus Placebo daily

Drug: Topiramate 100, Placebo

Topiramate 200, Placebo

EXPERIMENTAL

Topiramate 200 mg daily plus Placebo daily

Drug: Topiramate 200, Placebo

Topiramate 100, Aripiprazole 5

EXPERIMENTAL

Topiramate 100 daily plus, Aripiprazole 5mg daily

Drug: Topiramate 100, Aripiprazole 15; Drug: Topiramate 100, Aripiprazole 15mg

Topiramate 200, Aripiprazole 15

EXPERIMENTAL

Topiramate 200 mg daily plus Aripiprazole 15mg daily

Drug: Topiramate 200, Aripiprazole 15

Topiramate 100, Aripiprazole 7.5

EXPERIMENTAL

Topiramate 100 mg daily, Aripiprazole 7.5 mg daily

Drug: Topiramate 100, Aripiprazole 7.5

Topiramate 200, Aripiprazole 7.5mg

EXPERIMENTAL

Topiramate 200 mg daily plus Aripiprazole 7.5mg daily

Drug: Topiramate 200, Aripiprazole 7.5mg

Interventions

Double Placebo DRUG

1 capsule daily

Double Placebo

Aripiprazole 15, placebo DRUG

15 mg Aripiprazole daily plus placebo daily

Also known as: Abilify, Topamax

Aripiprazole 15, Placebo

Aripiprazole 7.5, Placebo DRUG

Aripiprazole 7.5 mg daily plus Placebo daily

Aripiprazole 7.5, Placebo

Topiramate 100, Placebo DRUG

Topiramate 100 mg daily plus Placebo daily

Topiramate 100mg, Placebo

Topiramate 200, Placebo DRUG

Topiramate 200 mg daily plus Placebo daily

Topiramate 200, Placebo

Topiramate 100, Aripiprazole 15 DRUG

Topiramate 100 mg daily plus Aripiprazole 15mg daily

Also known as: Abilify, Topamax

Topiramate 100, Aripiprazole 5

Topiramate 100, Aripiprazole 7.5 DRUG

Topiramate 100 mg daily plus Aripiprazole 7.5mg daily

Topiramate 100, Aripiprazole 7.5

Topiramate 100, Aripiprazole 15mg DRUG

Topiramate 100 mg daily plus Aripiprazole 15mg daily

Also known as: Abilify, Topamax

Topiramate 100, Aripiprazole 5

Topiramate 200, Aripiprazole 7.5mg DRUG

Topiramate 200 mg daily plus Aripiprazole 7.5mg daily

Also known as: Abilify, Topamax

Topiramate 200, Aripiprazole 7.5mg

Topiramate 200, Aripiprazole 15 DRUG

Topiramate 200mg daily plus Aripiprazole 15mg daily

Also known as: Abilify, Topamax

Topiramate 200, Aripiprazole 15

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• must be non-treatment seeking for alcohol dependence
• a current DSM-IV-TR diagnosis of alcohol dependence supported by the Structured Clinical Interview for DSM-IV-TR Axis I Disorders Patient Edition (SCID-I/P a minimum of ≥ 35drinks a week for men or ≥ 28 or more drinks a week for women
• must be suitable for outpatient treatment
• able to read English at an eighth grade level, understand their rights as provided by the informed consent, and be willing to sign an informed consent to participate in the study
• be between 21 and 65 years on age (inclusive)
• provide evidence of stable residence in the two months prior to enrollment and no plans to move for the next four months
• provide a verifiable contact person prior to randomization
• be in generally good health as determined by the physical exam, medical history, ECG and laboratory tests
• have a Body Mass Index \>18kg/m2 and \< 33 kg/m2
• if female, must be postmenopausal practicing an effective method of birth control, have negative pregnancy tests at randomization and before the ASAE;
• be willing to be adherent to medication dosing.

You may not qualify if:

• clinically significant medical abnormalities (i.e. ECG, hematological assessment, bilirubin \> 150% of the upper limit of normal or ALT or AST elevations \>300% the upper limit of normal, biochemistry including urinalysis, electrolytes,). (Persons with medical conditions that are adequately controlled by their primary care physician will not be excluded.)
• have significant alcohol withdrawal symptoms (clinical institute withdrawal assessment for alcohol revised (CIWA-Ar) \>10
• a history of suicide; history of renal impairment or nephrolithiasis; creatinine clearance of \<60 dl/minute
• pregnant or lactating or not using an adequate form of birth control
• taking other medications that may have an effect on alcohol consumption or are carbonic anhydrase inhibitors
• clinically significant diseases of the gastrointestinal system or active liver disease; subjects compelled to receive treatment to avoid imprisonment or loss of employment
• previously with a history of adverse reaction or hypersensitivity to either Topiramate or aripiprazole
• have a diagnosis of with schizophrenia or bipolar disorder and/or taking antipsychotics and other drugs that inhibit CYP3A4 or CYP2D6 isoenzymes
• history of seizures (e.g. epilepsy)
• patients currently diagnosed with a substance dependence diagnosis other than alcohol or tobacco
• patients who have participated in any clinical trial with an investigational agent within the past 30 days
• individuals with a reasonable expectation of being institutionalized during the course of the trial or pending legal charges
• pregnant or nursing women.

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead
• Brown University: collaborator

Study Sites (1)

Brown University Center for Addiction Studies

Providence, Rhode Island, 02903, United States

Location

Related Publications (1)

• Haass-Koffler CL, Goodyear K, Zywiak WH, Leggio L, Kenna GA, Swift RM. Comparing and Combining Topiramate and Aripiprazole on Alcohol-Related Outcomes in a Human Laboratory Study. Alcohol Alcohol. 2018 May 1;53(3):268-276. doi: 10.1093/alcalc/agx108.

  PMID: 29281033 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Aripiprazole; Topiramate

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Robert M Swift, MD, PhD

  Brown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Human Behavior

Study Record Dates

• First Submitted: April 20, 2009
• First Posted: April 21, 2009
• Study Start: September 1, 2007
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 7, 2015

Record last verified: 2015-10

Locations

US (1)