Imaging Dopamine Release in Depression

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-28

Study Completion Date

2017-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Dopamine Neurotransmission in Major Depression

NCT01659814

Major Depressive Disorder Anhedonia

COMPLETED

PET-MRI F-DOPA Activity in the Mesocorticolimbic System and Depressive Symptoms in the Prediction of Treatment Compatibility

NCT03026309

Depression

UNKNOWN

Depression and Dopamine Transporter Function Study Using C-11 Altropane

NCT01701141

Major Depressive Disorder Anhedonia

COMPLETED

PET Imaging Using the Tracer [18F]VAT to Assess the Antidepressant Effect of Nicotine.

NCT07095205

Major Depressive Disorder (MDD)

RECRUITING PHASE4

A Diagnosis and Treatment Optimization Study of Depression Based on the Neurological Mechanism of Reward System

NCT03148522

Diagnosis and Treatment of Depression

UNKNOWN NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Better understanding of the basic neurobiology of mood dysfunction appears necessary to enable further progress in the treatment of depression. Reward motivation (and the closely related construct of "reward learning") is a core neurobehavioral domain.(1,2) In major depressive disorder (MDD), low reward motivation is a key aspect of anhedonia, a cardinal symptom of MDD, and is related to resistance to treatment.(2,3) Although much has been learned about reward motivation's neurobiology and relevance to psychopathology, important gaps in our knowledge have impeded the application of basic science findings to improving treatment of MDD. Reward motivation in healthy subjects involves ventrostriatal (VST) dopamine (DA)(4,5), and reduced reward motivation is linked to MDD and anhedonia.(3,6) These data suggest that VST DA dysfunction might be present in MDD and manifested clinically by anhedonia. While DA neuroreceptor imaging studies have failed to verify this, they have been methodologically compromised. Limitations include imaging methods with poor resolution of functional striatal subregions, MDD samples heterogeneous for antidepressant use, and use of self-report measures of anhedonia, rather than objective behavioral testing of the specific domain of reward motivation. This will be the first study of both VST DA release (by PET imaging) and reward motivation, and will include patients with MDD and healthy volunteers. Reward motivation will be captured and operationalized as reward learning in a probabilistic reward task (prior to imaging). This will clarify if VST DA dysfunction is linked to impaired motivation in MDD. To test clinical implications in MDD patients, we will assess the relationship of VST DA release, reward motivation, and anhedonia to outcome of subsequent open label treatment with the DA D2 receptor agonist pramipexole.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Major Depressive Disorder

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Pramipexole

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

Group Type EXPERIMENTAL

Pramipexole

Intervention Type 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.

Healthy Control

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Pramipexole

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Mirapex (brand name)

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Family history of schizophrenia in parents, siblings, or children
* Ongoing cognitive-behavioral or interpersonal psychotherapy for depression (Supportive therapy is not an exclusion)
* Ongoing treatment with cimetidine

Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes