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Pathological GamblingPhase 2HFDEXNCT02203786

D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement

A Phase 2 study testing Haloperidol, Fluphenazine and Dexedrine in people with Pathological Gambling, run by Centre for Addiction and Mental Health at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Pathological Gambling
What is being tested?
Haloperidol, Fluphenazine and Dexedrine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteCanada
Study dates
Sep 2009to Sep 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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)
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Centre for Addiction and Mental Health

    Toronto, Ontario, M5S 2S1

Other trials in Canada

About this study

Official title: Comparative Effects of a D2 and Mixed D1-D2 Dopamine Antagonist on Gambling and Amphetamine Reinforcement in Pathological Gamblers and Healthy Controls

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.
Read the 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.

Being tested
Haloperidol, Fluphenazine, Dexedrine, Placebo, Slot Machine
Keywords
amphetamine, d1 and d2 receptors, dopamine antagonists, pathological gambling, priming, reinforcement
Medical subject headings
Gambling

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HaloperidolDrug

    Also called Teva-Haloperidol, DIN: 00396818, Haldol

    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.

  • FluphenazineDrug

    Also called APO-Fluphenazine, DIN: 00405345, Prolixin, Permitil

    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.

  • DexedrineDrug

    Also called Dextro-amphetamine sulphate, DIN: 01924516, D-amphetamine

    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.

  • PlaceboDrug

    Also called lactose capsule

    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.

  • Slot MachineBehavioural

    Also called reward cue

    15 minute play of a commercial slot machine game in bar-simulated laboratory setting.

Study groups in NCT02203786
Study groupRoleWhat they receive
HaloperidolActive comparatorSubjects 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.
Receives: Drug: Haloperidol; Drug: Dexedrine; Drug: Placebo; Behavioral: Slot Machine
FluphenazineActive comparatorSubjects 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.
Receives: Drug: Fluphenazine; Drug: Dexedrine; Drug: Placebo; Behavioral: Slot Machine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Subjective Reinforcement Self-report Scales

    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.

    Measured: 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).

Secondary outcomes (5)

  1. Diastolic Blood Pressure (DBP)

    Measure changes from baseline, especially physiologic reactivity to the slot machine and amphetamine.

    Measured: 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).

  2. Cognitive Task Performance

    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)

    Measured: At key points during testing: immediately after the slot machine, at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)

  3. Betting Behaviour in Laboratory-based Slot Machine Game

    Risk taking was operationally defined as credits wagered per spin (mean computed for total spins)

    Measured: 1x per test session (total of 4 test sessions) for duration of the study: 4 weeks (1 session/week)

  4. Speed of Play on Slot Machine Game

    Number of individual spins in a 15-minute slot machine game. Each spin corresponds to one wager.

    Measured: 15-minutes

  5. Winnings on Slot Machine Upon Completion of Game

    Credits

    Measured: 15-minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2014 (estimated)
  2. Study startSep 2009
  3. Primary completionJun 2015
  4. Study completionSep 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02203786
Sponsor's protocol ID
232-2009
Acronym
HFDEX
Status last verified
Apr 2016
First submitted
23 Jul 2014
Last updated
25 Apr 2016
Data monitoring committee
No
Individual data sharing
No

Publications

  • APA (2000) Diagnostic and Statistical Manual of Mental Disorders. IV-TR ed. American Psychiatric Association: Washington, DC.

  • Enggasser JL, de Wit H. Haloperidol reduces stimulant and reinforcing effects of ethanol in social drinkers. Alcohol Clin Exp Res. 2001 Oct;25(10):1448-56.

    PubMed 11696664

  • Holley FO, Magliozzi JR, Stanski DR, Lombrozo L, Hollister LE. Haloperidol kinetics after oral and intravenous doses. Clin Pharmacol Ther. 1983 Apr;33(4):477-84. doi: 10.1038/clpt.1983.65.

    PubMed 6831826

  • Lesieur HR, Blume SB. The South Oaks Gambling Screen (SOGS): a new instrument for the identification of pathological gamblers. Am J Psychiatry. 1987 Sep;144(9):1184-8. doi: 10.1176/ajp.144.9.1184.

    PubMed 3631315

  • Midha KK, McKay G, Edom R, Korchinski ED, Hawes EM, Hall K. Kinetics of oral fluphenazine disposition in humans by GC-MS. Eur J Clin Pharmacol. 1983;25(5):709-11. doi: 10.1007/BF00542363.

    PubMed 6662169

  • Wachtel SR, Ortengren A, de Wit H. The effects of acute haloperidol or risperidone on subjective responses to methamphetamine in healthy volunteers. Drug Alcohol Depend. 2002 Sep 1;68(1):23-33. doi: 10.1016/s0376-8716(02)00104-7.

    PubMed 12167550

  • Wong YN, Wang L, Hartman L, Simcoe D, Chen Y, Laughton W, Eldon R, Markland C, Grebow P. Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers. J Clin Pharmacol. 1998 Oct;38(10):971-8. doi: 10.1002/j.1552-4604.1998.tb04395.x.

    PubMed 9807980

  • Zack M, Lobo D, Biback C, Fang T, Smart K, Tatone D, Kalia A, Digiacomo D, Kennedy JL. Priming effects of a slot machine game and amphetamine on probabilistic risk-taking in people with gambling disorder and healthy controls. J Clin Exp Neuropsychol. 2023 Feb;45(1):31-60. doi: 10.1080/13803395.2023.2187041. Epub 2023 Mar 15.

    PubMed 36919514

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Haloperidol, Fluphenazine and Dexedrine in people with Pathological Gambling, run by Centre for Addiction and Mental Health at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02203786, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2016.

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