The Effects of Dopamine on Reward Processing

This study is currently recruiting participants.
Verified October 2013 by Mclean Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Diego A. Pizzagalli, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01253421
First received: December 1, 2010
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to evaluate the effects of a single low dose of the D2/D3 antagonist amisulpride on reward processing. More generally, this study will test the role of dopamine (a naturally occurring brain chemical) in depression.

Hypotheses:

Administration of a single low dose of the D2/D3 antagonist amisulpride will (1) improve performance in a behavioral task assessing learning from feedback and (2) boost activation in reward-related brain regions.


Condition Intervention
Major Depressive Disorder (MDD)
Drug: Amisulpride
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of Dopamine on Reward Processing

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Performance on a behavioral task assessing learning from positive and negative feedback. [ Time Frame: one-time task, administered during session 2 ] [ Designated as safety issue: No ]
  • Brain activation during a task involving monetary rewards. [ Time Frame: one-time task, administered at session 2 ] [ Designated as safety issue: No ]
  • Brain activation to social positive and negative feedback [ Time Frame: second session ] [ Designated as safety issue: No ]
    Brain activation to social positive and negative feedback


Secondary Outcome Measures:
  • Ratings of mood and affect. [ Time Frame: administered at sessions 1 and 2 ] [ Designated as safety issue: No ]

Estimated Enrollment: 72
Study Start Date: February 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Amisulpride
single low-dose pharmacological challenge, 50 mg amisulpride capsule
Drug: Amisulpride
single low-dose pharmacological challenge, 50 mg amisulpride
Other Name: Solian
Placebo Comparator: Placebo
single-dose placebo capsule
Drug: Placebo
single-dose placebo capsule

Detailed Description:

Through an integration of an fMRI approach coupled with a pharmacological challenge, the goal of the current study will be to investigate the role of dopamine in MDD. Participants in this research will include 36 MDD subjects and 36 demographically matched healthy participants recruited from the community by Dr. Pizzagalli's laboratory at McLean Hospital's Center for Depression, Anxiety and Stress Research. This study will include two sessions:

  • The first session will involve a diagnostic interview, and a series of questionnaires and assessments.
  • The second session will take place at the McLean Hospital's Neuroimaging Center, and include the administration of a low-dose of amisulpride (50 mg capsule) or placebo, followed by an fMRI brain scan and administration of two behavioral tasks.
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Inclusion Criteria for MDD Subjects:

    1. Diagnostic and Statistical Manual of Mental Disorders (DSM IV) diagnostic criteria for MDD, diagnosed with the use of the Structured Clinical Interview for DSM Disorders (SCID);
    2. Written informed consent;
    3. Both genders and all ethnic origins, age between 18 and 45;
    4. A baseline HRSD score > 16 (17-item version);
    5. Right-handed.
    6. Absence of any psychotropic medications for at least 2 weeks:

      • 6 weeks for fluoxetine,
      • 6 months for neuroleptics,
      • 2 weeks for benzodiazepines,
      • 2 weeks for any other antidepressants.

Inclusion Criteria for Control Subjects:

  1. Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (SCID-I/NP);
  2. Written informed consent;
  3. Both genders and all ethnic origins, age between 18 and 45;
  4. Right-handed;
  5. Absence of any medications for at least 3 weeks;
  6. Absence of pregnancy.

Exclusion Criteria:

  • Exclusion Criteria for All Subjects:

    1. Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment;
    2. Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, or partner with vasectomy);
    3. Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological or hematologic disease;
    4. Lifetime history of seizure disorder;
    5. Lifetime history or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse; which will lead to exclusion); simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD;
    6. Lifetime history of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine);
    7. Lifetime history of use of dopaminergic drugs (including methylphenidate);
    8. Lifetime history or current diagnosis of dementia, or a score of < 26 on the Mini Mental Status Examination at the screening visit;
    9. Lifetime history of adverse drug reactions or allergy to the study drug (amisulpride);
    10. Patients with mood congruent or mood incongruent psychotic features;
    11. Current use of other psychotropic drugs;
    12. Clinical or laboratory evidence of hypothyroidism;
    13. Patients with a lifetime history of electroconvulsive therapy (ECT);
    14. Patients with renal insufficiency;
    15. Failure to meet standard MRI safety requirements
    16. Electrolytes, BUN, Creatinine: outside the normal range (also ruling out renal insufficiency);
    17. Liver function tests (SGOT, SGPT, CPK, alkaline phosphatase, total bilirubin) above 1.5X upper normal;
    18. QTc interval in EKG above 450 ms or EKG indicative of arrhythmia or cardiac conduction abnormalities;
    19. Diabetes with poor glucose control;
    20. Cardiac disease, bradycardia less than 55 bpm, hypokalemia, congenital prolongation of QT interval or on-going treatment with a medication likely to induce one of these conditions.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01253421

Contacts
Contact: Laura M Murray, BA 617-855-4236 lmurray@mclean.harvard.edu
Contact: Andrew L Cohen, BS 617-855-4237 acohen@mclean.harvard.edu

Locations
United States, Massachusetts
McLean Hospital Recruiting
Belmont, Massachusetts, United States, 02478
Contact: Laura M Murray, BA    617-855-4236    lmurray@mclean.harvard.edu   
Contact: Andrew L Cohen, BS    617-855-4237    acohen@mclean.harvard.edu   
Principal Investigator: Diego A Pizzagalli, PhD         
Sponsors and Collaborators
Mclean Hospital
Investigators
Principal Investigator: Diego A Pizzagalli, PhD McLean Hospital, Harvard University
  More Information

No publications provided

Responsible Party: Diego A. Pizzagalli, Director, Center for Depression, Anxiety and Stress Research, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01253421     History of Changes
Other Study ID Numbers: 2010-P001568, R01MH068376
Study First Received: December 1, 2010
Last Updated: October 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mclean Hospital:
MDD
Major Depressive Disorder
Amisulpride

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Dopamine
Sultopride
Sulpiride
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Psychotropic Drugs
Dopamine Antagonists
Antidepressive Agents, Second-Generation
Antidepressive Agents

ClinicalTrials.gov processed this record on April 17, 2014