Imaging Dopamine Release in Depression

NCT02033369 | Completed Phase 4 Results DMC

• 2 other identifiers: #68531R01MH099322-01A1
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine whether ventral striatal dopamine release is a mechanism of reward motivation in major depression, whether dopamine release is low in depression, and whether DA release and reward motivation predict response to dopamine-targeted treatment with pramipexole.

Conditions

Major Depressive Disorder

Keywords

Major depressive disorder; MDD; depression; pramipexole

Outcome Measures

Primary Outcomes (1)

• Change in Hamilton Rating Scale for Depression

  Hamilton Rating Scale for Depression (HRSD), 17-item version. This standard scale will be used to assess severity of depression, looking at change in total score from baseline to week 6, rating severity of depression on a scale from 0 (least depression) to 50 (greatest depression)

  Baseline and 6 weeks

Secondary Outcomes (6)

• Change in Snaith Hamilton Pleasure Scale

  Baseline and 6 weeks

• Change in Temporal Experience of Pleasure Scale - Anticipatory Subscale

  Baseline and 6 weeks

• Change in Mood and Anxiety Symptom Questionnaire, Short Form

  Baseline and 6 weeks

• Change in the Apathy Evaluation Rating Scale

  Baseline and 6 weeks

• Change in Clinical Global Improvement - Severity Scale

  6 weeks

Study Arms (2)

Pramipexole

EXPERIMENTAL

Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg.

Drug: Pramipexole

Healthy Control

NO INTERVENTION

Healthy volunteers were matched to MDD group subjects by age, gender, and ethnicity, and will have no lifetime psychiatric disorders.

Interventions

Pramipexole DRUG

Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day.

Also known as: Mirapex (brand name)

Pramipexole

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Weight between 44 kg and 115 kg
• Meets DSM-IV criteria for principal diagnosis of MDD, current major depressive episode, without psychotic features
• Score of \>16 and \<29 on 17-item Hamilton Rating Scale for Depression
• Psychotropic-naïve, as defined by lifetime \<2 weeks treatment with antidepressants, anxiolytics or antipsychotics
• Able to tolerate a treatment-free period during study participation
• Able to provide informed consent

You may not qualify if:

• A principal diagnosis of any current Axis I psychiatric disorder other than the MDD
• Lifetime diagnosis of any psychotic disorder, bipolar disorder, mental retardation, attention deficit/hyperactivity disorder, or substance use disorders (including nicotine use disorders)
• Serious suicidal risk or history of violent behavior which would make participation in the protocol unsafe
• Any tobacco use in the prior three months (if not already excluded for abuse/dependence by #1)
• Illicit drug use in the prior three months, as evidenced by history or urine toxicology screen
• Women who are pregnant, nursing, postmenopausal, or using hormonal methods of birth control
• Women who are not using an effective birth control method or sexual abstinence during the ten days before the scan
• Any medical or neurological problem that might affect interpretation of findings or safety of participation (e.g., blood dyscrasias, lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, malignancy, neurological diseases of the brain, history of seizures or head trauma), low hemoglobin (Hb \< 12 gm/dL in males, Hb \< 10.5 gm/dL in females))
• Blood donation within 4 weeks of study
• Metal implants or paramagnetic objects in the body that might affect safety of undergoing MRI (e.g., heart pacemaker, shrapnel, bullets, surgical prostheses or surgical clips), as determined in consultation with a neuroradiologist and according to the guidelines set forth in the reference: "Guide to MR procedures and metallic objects" Shellock; Lippincott Williams and Wilkins, NY, 2001
• More than one major risk factor for coronary artery disease (e.g. hyperlipidemia, sedentary lifestyle). Smokers are already excluded by #4 above, and diabetics by #8 above
• Systolic blood pressure \> 140 or diastolic blood pressure \> 90 based on at least two readings at rest
• History of untoward reaction to amphetamine or other stimulant medication, or pramipexole
• Any psychotropic treatment in the past 3 weeks (or depot medication in the past 6 months), except for lorazepam,which may be administered as needed prior to imaging day
• Current, past or anticipated exposure to radiation in the workplace, or participation in nuclear medicine procedures, including research protocols (In case of previous exposure to activity due to research studies, subjects will be eligible if all conditions listed below are fulfilled: 1) The injected dose and dosimetry of the radiotracer are known; 2) Except for research studies, the subject has not been exposed to radiation (workplace and medical); 3) Adding prior exposure to the exposure due to the study will result in a yearly cumulative exposure lower than the FDA limit for research studies

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• Columbia University: collaborator
• Research Foundation for Mental Hygiene, Inc.: collaborator
• Mclean Hospital: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (8)

• Sanislow CA, Pine DS, Quinn KJ, Kozak MJ, Garvey MA, Heinssen RK, Wang PS, Cuthbert BN. Developing constructs for psychopathology research: research domain criteria. J Abnorm Psychol. 2010 Nov;119(4):631-9. doi: 10.1037/a0020909.

  PMID: 20939653 BACKGROUND

• Treadway MT, Zald DH. Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev. 2011 Jan;35(3):537-55. doi: 10.1016/j.neubiorev.2010.06.006. Epub 2010 Jul 11.

  PMID: 20603146 BACKGROUND

• Vrieze E, Pizzagalli DA, Demyttenaere K, Hompes T, Sienaert P, de Boer P, Schmidt M, Claes S. Reduced reward learning predicts outcome in major depressive disorder. Biol Psychiatry. 2013 Apr 1;73(7):639-45. doi: 10.1016/j.biopsych.2012.10.014. Epub 2012 Dec 8.

  PMID: 23228328 BACKGROUND

• Forbes EE, Hariri AR, Martin SL, Silk JS, Moyles DL, Fisher PM, Brown SM, Ryan ND, Birmaher B, Axelson DA, Dahl RE. Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. Am J Psychiatry. 2009 Jan;166(1):64-73. doi: 10.1176/appi.ajp.2008.07081336. Epub 2008 Dec 1.

  PMID: 19047324 BACKGROUND

• Kumar P, Waiter G, Ahearn T, Milders M, Reid I, Steele JD. Abnormal temporal difference reward-learning signals in major depression. Brain. 2008 Aug;131(Pt 8):2084-93. doi: 10.1093/brain/awn136. Epub 2008 Jun 25.

  PMID: 18579575 BACKGROUND

• Pizzagalli DA, Iosifescu D, Hallett LA, Ratner KG, Fava M. Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task. J Psychiatr Res. 2008 Nov;43(1):76-87. doi: 10.1016/j.jpsychires.2008.03.001. Epub 2008 Apr 22.

  PMID: 18433774 BACKGROUND

• Whitton AE, Reinen JM, Slifstein M, Ang YS, McGrath PJ, Iosifescu DV, Abi-Dargham A, Pizzagalli DA, Schneier FR. Baseline reward processing and ventrostriatal dopamine function are associated with pramipexole response in depression. Brain. 2020 Feb 1;143(2):701-710. doi: 10.1093/brain/awaa002.

  PMID: 32040562 DERIVED

• Schneier FR, Slifstein M, Whitton AE, Pizzagalli DA, Reinen J, McGrath PJ, Iosifescu DV, Abi-Dargham A. Dopamine Release in Antidepressant-Naive Major Depressive Disorder: A Multimodal [11C]-(+)-PHNO Positron Emission Tomography and Functional Magnetic Resonance Imaging Study. Biol Psychiatry. 2018 Oct 15;84(8):563-573. doi: 10.1016/j.biopsych.2018.05.014. Epub 2018 May 25.

  PMID: 30041971 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Pramipexole

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Franklin Schneier, MD
• Organization: NYSPI

fschneier@nyspi.columbia.edu

646-774-8041

Study Officials

• Franklin Schneier, MD

  NYSPI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 9, 2014
• First Posted: January 10, 2014
• Study Start: February 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: July 1, 2017
• Last Updated: November 1, 2019
• Results First Posted: November 21, 2017

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)