PILOT-PRAXOL: Pramipexole to Target "Anhedonic Depression"

Sponsor

Region Skane (Other)

Overall Status

Completed

CT.gov ID

NCT04121091

Collaborator

Lund University (Other)

Enrollment

Location

Arm

17.4

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The heterogeneity of depression suggests that different neurocircuits and pathophysiological mechanisms are involved. Anhedonia - the inability to experience pleasure from, or the lack of motivation to carry out, usually enjoyable activities - is an endophenotype within the depression spectrum, with a distinct pathophysiology of dopaminergic mesolimbic projections. Anhedonia is common in depression and associated with treatment resistance. Pramipexole, an agonist to the dopamine -receptor 3, is an established treatment of Parkinson's disease. Based on its mechanism of action, pramipexole might be efficacious in a subtype of depression characterized by anhedonia and lack of motivation - symptoms linked to dopaminergic hypofunction. In this proof-of-concept pilot study the investigators test the anti-anhedonic and antidepressant effects of add-on pramipexole using an "enriched population study design" including only depressed patients with significant anhedonia. To understand the neurobiology of anhedonia in depression and to identify treatment predictors, the investigators also do assessments of anhedonia-related neurocircuitry using (f)MRI and blood biomarkers.

Condition or Disease	Intervention/Treatment	Phase
Depression, Bipolar Depression, Unipolar Dysthymia Anhedonia	Drug: Pramipexole Pill	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pramipexole Augmentation to Target Anhedonia in Depression - a Pilot Study

Actual Study Start Date :

Oct 4, 2019

Actual Primary Completion Date :

Mar 18, 2021

Actual Study Completion Date :

Mar 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pramipexole	Drug: Pramipexole Pill Add-on pramipexole

Arm

Intervention/Treatment

Experimental: Pramipexole

Drug: Pramipexole Pill

Add-on pramipexole

Outcome Measures

Primary Outcome Measures

Dimensional Anhedonia Rating Scale (DARS) score [baseline to week 10]
Change in anhedonia symptoms (total score on the DARS). The range is 0-68, lower score indicating more severe anhedonia.

Secondary Outcome Measures

Response/remission [baseline to week 10]
Montgomery Åsberg Depression Rating Scale (MADRS) reduction 50%, MADRS ≤ 10 respectively
Montgomery Åsberg Depression Rating Scale (MADRS) score [baseline to week 10]
Change in depression symptoms (total score on the MADRS)
Snaith-Hamilton Anhedonia Pleasure Scale [baseline to week 10]
Change in anhedonia symptoms (total score on the Snaith-Hamilton Anhedonia Pleasure Scale)
the Motivation and Pleasure Scale [baseline to week 10]
Change in motivation/anhedonia symptoms (total score on the the Motivation and Pleasure Scale)
Generalized Anxiety Disorder-7 [baseline to week 10]
Change in anxiety symptoms (total score on the the Generalized Anxiety Disorder-7 scale)
Insomnia Severity Index [baseline to week 10]
Change in insomnia symptoms (total score on the the Insomnia Severity Index scale)
Fatigue Severity Scale [baseline to week 10]
Change in fatigue symptoms (total score on the the Fatigue Severity scale)
The Apathy Evaluation Scale [baseline to week 10]
Change in apathy symptoms (total score on the the The Apathy Evaluation Scale)
Change in inflammatory biomarkers [baseline to week 10]
The investigators will measure blood levels of Interleukin-6, C-reactive protein, Tumor Necrosis Factor Alpha, and White Blood Cell count at baseline and at study completion. The investigators will test if baseline levels and treatment-associated change in inflammatory markers can predict treatment response
Change in brain imaging parameters [baseline to week 10 (and baseline data as potential predictor)]
Structural imaging, followed by resting-state functional imaging, diffusion tensor imaging and thereafter the monetary incentive delay task

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 and ≤75.
Diagnosis of unipolar depression; bipolar disorder in depressive phase or dysthymia.
Symptoms of depression; Total-score ≥ 18, measured by Montgomery-Åsberg Depression Rating Scale (MADRS).
Symptoms of anhedonia; Total-score < 27, measured by Dimensional Anhedonia Rating Scale (DARS).
Ongoing treatment with at least one antidepressant drug ≥ 4 weeks without major changes in dosage. Patients with bipolar disorder must have a mood-stabilizing drug treatment.
Must sign an informed consent. -

Exclusion Criteria:

Ongoing pregnancy, breastfeeding or planning for pregnancy.
High suicidality assessed by the researcher with medical degree.
Ongoing substance use disorder (last 12 month).
Diagnosis of psychosis.
Ongoing involuntary psychiatric treatment.
History of Impulse-control disorder or current ADHD diagnosis.
Diagnosis of Intellectual disability, dementia, or other circumstances leading to difficulties to understand the implications of participating in the study and to give informed consent.
Diagnosis of renal failure (eGFR < 50 ml/min/1,73 m2 ) or severe cardiovascular disease (defined as symptoms of heart failure NYHA class 2).
Recently committed to psychotherapy (during the last 6 weeks) or planning for psychotherapy during the participation of the study.
Ongoing ECT-treatment.
Other diseases, disorders or medical treatments that according to the researchers might influence the results of the study or increases the risks of the study. Such as Parkinson's disorder, liver failure, cancer not in remission (for at least over a year).
Confirmed or suspected allergy to the active substance or excipients of the drug used in this study.
Committed to other trials
Other reasons that according to the researcher might prevent the subject to fulfill the obligations of the study. For example insufficient drug compliance. -