Pramipexole to Target "Anhedonic Depression" (PILOT-PRAXOL)

Pramipexole Augmentation to Target Anhedonia in Depression - a Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Anhedonia; Depression, Unipolar; Dysthymia; Depression, Bipolar
• Intervention / Treatment: Drug: Pramipexole Pill

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 22358
    • Psychiatry Clinic, Lund, Region Skåne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 and ≤75.
2. Diagnosis of unipolar depression; bipolar disorder in depressive phase or dysthymia.
3. Symptoms of depression; Total-score ≥ 18, measured by Montgomery-Åsberg Depression Rating Scale (MADRS).
4. Symptoms of anhedonia; Total-score < 27, measured by Dimensional Anhedonia Rating Scale (DARS).
5. 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.
6. Must sign an informed consent. -

Exclusion Criteria:

1. Ongoing pregnancy, breastfeeding or planning for pregnancy.
2. High suicidality assessed by the researcher with medical degree.
3. Ongoing substance use disorder (last 12 month).
4. Diagnosis of psychosis.
5. Ongoing involuntary psychiatric treatment.
6. History of Impulse-control disorder or current ADHD diagnosis.
7. 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.
8. Diagnosis of renal failure (eGFR < 50 ml/min/1,73 m2 ) or severe cardiovascular disease (defined as symptoms of heart failure NYHA class 2).
9. Recently committed to psychotherapy (during the last 6 weeks) or planning for psychotherapy during the participation of the study.
10. Ongoing ECT-treatment.
11. 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).
12. Confirmed or suspected allergy to the active substance or excipients of the drug used in this study.
13. Committed to other trials
14. Other reasons that according to the researcher might prevent the subject to fulfill the obligations of the study. For example insufficient drug compliance. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response/remission	Montgomery Åsberg Depression Rating Scale (MADRS) reduction 50%, MADRS ≤ 10 respectively	baseline to week 10
Montgomery Åsberg Depression Rating Scale (MADRS) score	Change in depression symptoms (total score on the MADRS)	baseline to week 10
Snaith-Hamilton Anhedonia Pleasure Scale	Change in anhedonia symptoms (total score on the Snaith-Hamilton Anhedonia Pleasure Scale)	baseline to week 10
the Motivation and Pleasure Scale	Change in motivation/anhedonia symptoms (total score on the the Motivation and Pleasure Scale)	baseline to week 10
Generalized Anxiety Disorder-7	Change in anxiety symptoms (total score on the the Generalized Anxiety Disorder-7 scale)	baseline to week 10
Insomnia Severity Index	Change in insomnia symptoms (total score on the the Insomnia Severity Index scale)	baseline to week 10
Fatigue Severity Scale	Change in fatigue symptoms (total score on the the Fatigue Severity scale)	baseline to week 10
The Apathy Evaluation Scale	Change in apathy symptoms (total score on the the The Apathy Evaluation Scale)	baseline to week 10
Change in inflammatory biomarkers	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	baseline to week 10
Change in brain imaging parameters	Structural imaging, followed by resting-state functional imaging, diffusion tensor imaging and thereafter the monetary incentive delay task	baseline to week 10 (and baseline data as potential predictor)

Collaborators and Investigators

• Sponsor: Region Skane
• Collaborators: Lund University

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2019
• Primary Completion (Actual): March 18, 2021
• Study Completion (Actual): March 18, 2021

Study Registration Dates

• First Submitted: October 4, 2019
• First Submitted That Met QC Criteria: October 8, 2019
• First Posted (Actual): October 9, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 14, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Bipolar and Related Disorders; Depression; Depressive Disorder; Anhedonia; Bipolar Disorder; Dysthymic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: 2019-001907-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No