Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement (HFDEX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02203786
Recruitment Status : Completed
First Posted : July 30, 2014
Results First Posted : April 25, 2016
Last Update Posted : April 25, 2016
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Daniela Lobo, Centre for Addiction and Mental Health

Brief Summary:

To determine if:

  1. pathological gambling is similar to psychostimulant addiction as reflected by parallel roles for D1 and D2 receptors in gambling and stimulant reinforcement.
  2. these parallel roles are linked with gambling pathology or if they are evident in both gamblers and controls.

Condition or disease Intervention/treatment Phase
Pathological Gambling Drug: Haloperidol Drug: Fluphenazine Drug: Dexedrine Drug: Placebo Behavioral: Slot Machine Phase 2

Detailed Description:

BACKGROUND: No previous research appears to have investigated the role of dopamine (DA) D1 or D2 receptors in psychostimulant reinforcement in pathological gamblers. Effects of haloperidol vs. placebo will reveal the role of D2 and the effects of fluphenazine vs. haloperidol will reveal the role of D1 in this process.

OBJECTIVE: This study will begin to define the neurochemistry of Pathological Gambling by examining the roles of dopamine D1 and D2 receptors in gambling reinforcement and psychostimulant reinforcement, and exploring genetic predictors of response to DA probes in Pathological Gambling subjects (subjects) and healthy controls.

METHODS: A double-blind, placebo controlled, counterbalanced between-within design will be employed. Each participant will attend 4 sessions with a minimum of 1 week between sessions to ensure drug washout. Responses to the slot machine will be assessed in sessions 1 and 2 (Phase I), and responses to amphetamine will be assessed in sessions 3 and 4 (Phase II). A second capsule (dummy) will be administered at expected peak levels for each antagonist on sessions 1 and 2 to standardize the procedure across sessions.

Subjective reinforcement self-report scales will be administered at key intervals throughout the study.

HYPOTHESIS: It is hypothesized that haloperidol (3-mg) will increase priming (Desire to Gamble, Gambling word salience) and pleasurable effects (e.g., Enjoyment/Liking) induced by playing a slot machine in Pathological Gambling subjects (N = 40). If gambling and stimulant reinforcement are mediated by common mechanisms, haloperidol will also increase priming and pleasurable effects of amphetamine (20-mg) in Pathological Gambling subjects.

If D1 mediates effects of haloperidol, the mixed D1-D2 antagonist, fluphenazine (fluphenazine; 3-mg) will decrease or not alter responses to the slot machine and amphetamine in Pathological Gambling subjects. If D2 deficits are linked with gambling pathology, haloperidol will not affect slot machine or amphetamine reinforcement in controls (N= 40).

If D1 deficits are linked with gambling pathology, fluphenazine will increase gambling and amphetamine reinforcement in controls, by mitigating undue D1 activation in subjects with high baseline D1 function. If D1 or D2 genes contribute to gambling or amphetamine reinforcement, genotype will predict responses to the manipulations.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Comparative Effects of a D2 and Mixed D1-D2 Dopamine Antagonist on Gambling and Amphetamine Reinforcement in Pathological Gamblers and Healthy Controls
Study Start Date : September 2009
Actual Primary Completion Date : June 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Haloperidol

Subjects randomized to pre-treatment drug sequence 1 (haloperidol on day 1 of each phase), or drug sequence 2 (haloperidol on day 2 of each phase).

Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol OR 3 visually identical placebo (lactose) capsules

Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.

Response measured to 15 min session of a commercial slot machine game.

Drug: Haloperidol

Dose/maximum dose = 3-mg; route = oral. Participants assigned to the haloperidol antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).

Dose 1: 3 visually identical capsules, each containing 1 mg haloperidol.

Other Names:
  • Teva-Haloperidol
  • DIN: 00396818
  • Haldol

Drug: Dexedrine

Dose/maximum dose = 20-mg; route = oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.

Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg D-amphetamine.

Other Names:
  • Dextro-amphetamine sulphate
  • DIN: 01924516
  • D-amphetamine

Drug: Placebo

Dose 1: On alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing) participants will receive 3 visually identical placebo (lactose) capsules.

Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1.

Other Name: lactose capsule

Behavioral: Slot Machine
15 minute play of a commercial slot machine game in bar-simulated laboratory setting.
Other Name: reward cue

Active Comparator: Fluphenazine

Subjects randomized to pre-treatment drug sequence 1 (fluphenazine on day 1 of each phase), or drug sequence 2 (fluphenazine on day 2 of each phase).

Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine OR 3 visually identical placebo (lactose) capsules

Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg dexedrine.

Response measured to 15 min session of a commercial slot machine game.

Drug: Fluphenazine

Dose/maximum dose = 3-mg; route = oral. Participants assigned to the fluphenazine antagonist group will receive 2 doses (@ 3 mg) on alternate sessions (with minimum of 2 weeks between individual doses).

Dose 1: 3 visually identical capsules, each containing 1 mg fluphenazine.

Other Names:
  • APO-Fluphenazine
  • DIN: 00405345
  • Prolixin
  • Permitil

Drug: Dexedrine

Dose/maximum dose = 20-mg; route = oral. All participants will receive 2 doses (@ 20 mg) during Phase II - sessions 3, 4, with minimum 1 week between individual doses.

Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 3 and 4 (Phase II), the dose will consist of 2 visually identical capsules each containing 10 mg D-amphetamine.

Other Names:
  • Dextro-amphetamine sulphate
  • DIN: 01924516
  • D-amphetamine

Drug: Placebo

Dose 1: On alternate sessions (1 and 3 or 2 and 4, depending on counterbalancing) participants will receive 3 visually identical placebo (lactose) capsules.

Dose 2: when participants reach expected peak blood levels for dose 1, they will receive their second dose. On sessions 1 and 2 (Phase I), this will consist of 2 dummy capsules, visually identical to those administered for dose 1.

Other Name: lactose capsule

Behavioral: Slot Machine
15 minute play of a commercial slot machine game in bar-simulated laboratory setting.
Other Name: reward cue




Primary Outcome Measures :
  1. Subjective Reinforcement Self-report Scales [ Time Frame: At key points in testing: immediately after the slot machine game, and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration). ]
    Self-reported Confidence to Refrain from Gambling (0 - 10) was assessed at test session baseline, before the slot machine and after the slot machine (Phase 1); and before amphetamine and at peak amphetamine (Phase 2). The maximum score (10) denotes complete confidence to refrain from gambling (i.e., NO urge or compulsion to gamble); the minimum score (0) denotes complete lack of confidence to refrain from gambling (i.e., overwhelming urge to gamble). Scores between 10 and 0 denote intermediate confidence to refrain from gambling with LOWER scores denoting less confidence to refrain from gambling -- i.e., GREATER urge or compulsive motivation to gamble. Scores shown are based on single item visual analogue ratings 0-10 from each participant at the specified time point. The mean (SD) of these single item ratings is presented for each sub-group.


Secondary Outcome Measures :
  1. Diastolic Blood Pressure (DBP) [ Time Frame: At key points in testing: immediately after the slot machine game (change from session baseline), and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)(change from session baseline). ]
    Measure changes from baseline, especially physiologic reactivity to the slot machine and amphetamine.

  2. Cognitive Task Performance [ Time Frame: At key points during testing: immediately after the slot machine, at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration) ]
    Response time to words (gambling, alcohol, positive affect, negative affect) as a percentage of neutral categorized words (parts of a building). This provides an index of the relative salience of stimuli from these four categories against a baseline of reaction to words with no clinical relevance or emotional valence. Smaller scores indicate faster relative response time to the test stimuli vs. neutral stimuli (i.e., greater salience)

  3. Betting Behaviour in Laboratory-based Slot Machine Game [ Time Frame: 1x per test session (total of 4 test sessions) for duration of the study: 4 weeks (1 session/week) ]
    Risk taking was operationally defined as credits wagered per spin (mean computed for total spins)

  4. Speed of Play on Slot Machine Game [ Time Frame: 15-minutes ]
    Number of individual spins in a 15-minute slot machine game. Each spin corresponds to one wager.

  5. Winnings on Slot Machine Upon Completion of Game [ Time Frame: 15-minutes ]
    Credits



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   19 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • PATHOLOGICAL GAMBLERS
  • otherwise healthy, non-treatment seeking, non-abstinent
  • male or female
  • ages 19-65
  • DSM-IV PG symptom scale score > 5
  • SOGS (South Oaks Gambling Screen) score > 5
  • nicotine dependence acceptable
  • CONTROLS
  • healthy
  • male or female
  • ages 19-65
  • DSM-IV PG symptom scale score = 0
  • SOGS score = 0
  • nicotine dependence acceptable
  • must have played slot machine > 5 times

Exclusion Criteria:

  • both Pathological Gamblers and Controls
  • Axis I psychopathology aside from nicotine dependence (or PG) based on SCID
  • Schizotypal or Borderline Personality Disorder based on psychiatric interview
  • Family history of schizophrenia or bipolar disorder
  • English comprehension below grade 7 level.
  • ADS (Alcohol Dependence Scale) > 13 (more than low dependence)
  • BDI (Beck Depression Inventory) short form > 10 (more than low depression)
  • DAST (Drug Abuse Screening Test) > 4 (possible drug abuse)
  • Consumption of > 20/15 (men/women) standard alcoholic drinks/ week (hazardous drinking)
  • Smoking > 20 cigarettes/day to help minimize withdrawal symptoms during test phase
  • Any prior use of psychostimulant drugs
  • Current use of medication that could interact with any of the study medications
  • Women who are pregnant or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02203786


Locations
Layout table for location information
Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5S 2S1
Sponsors and Collaborators
Centre for Addiction and Mental Health
Canadian Institutes of Health Research (CIHR)
Investigators
Layout table for investigator information
Principal Investigator: Daniela Lobo, MD, Ph.D. Centre for Addiction and Mental Health

Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Daniela Lobo, Clinician Scientist, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT02203786     History of Changes
Other Study ID Numbers: 232-2009
First Posted: July 30, 2014    Key Record Dates
Results First Posted: April 25, 2016
Last Update Posted: April 25, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Daniela Lobo, Centre for Addiction and Mental Health:
amphetamine
d1 and d2 receptors
dopamine antagonists
pathological gambling
priming
reinforcement
Additional relevant MeSH terms:
Layout table for MeSH terms
Amphetamine
Dextroamphetamine
Gambling
Disruptive, Impulse Control, and Conduct Disorders
Mental Disorders
Dopamine
Haloperidol
Haloperidol decanoate
Fluphenazine
Fluphenazine depot
Fluphenazine enanthate
Dopamine Antagonists
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antiemetics
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Dyskinesia Agents
Central Nervous System Stimulants
Adrenergic Agents