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| Name | Class |
|---|---|
| Lund University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pramipexole | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pramipexole Pill | Drug | Add-on pramipexole |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Response | Montgomery Åsberg Depression Rating Scale (MADRS). The range is 0-60, lower score indicating less general depressive symptoms. Response definition: reduction of at least 50% Remission definition: MADRS total score equal to or below 10 | baseline to week 10 |
| Montgomery Åsberg Depression Rating Scale (MADRS) Score |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Psychiatry Clinic, Lund, Region Skåne | Lund | 22358 | Sweden |
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12 patients with unipolar or bipolar, moderate-to-severe, depression were assigned to active open-label treatment with pramipexole. The sample was enriched for significant anhedonia symptoms, enrolling only patients with a score of <27 on the Dimensional Anhedonia Rating Scale (DARS, inverse scale). 1 dropout pre-assignment/pre-treatment.
Patients were recruited from outpatient clinics in Lund, Sweden. All study visits were conducted via the adult psychiatric clinic in Lund, Baravägen 1, 221 85, Lund during the period 4 Oct 2019 - 18 Mar 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pramipexole | Active treatment, open-label, with the dopamine agonist pramipexol individually titrated to highest tolerable dose (max 4,5 mg salt) daily. Administration: tablets orally. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Open-label, only one arm
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| ID | Title | Description |
|---|---|---|
| BG000 | Pramipexole | 12 patients |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | baseline to week 10 |
|
|
For each participant, adverse event data was collected for 14 weeks: every week for 10 weeks and an additional check-up at week 14.
According to EU regulation 536/2014 (Clinical Trials Regulation, CTR).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pramipexole | Pramipexole Pill: Add-on pramipexole | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment |
Inherent limitations and caveats of this test-of-feasibility study: small-scale (small sample) and open-label design.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Daniel Lindqvist | Unit of Biological and Precision Psychiatry | +4646173885 | daniel.lindqvist@med.lu.se |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 17, 2019 | Oct 10, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| D003866 | Depressive Disorder |
| D019263 | Dysthymic Disorder |
| D059445 | Anhedonia |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D019954 | Neurobehavioral Manifestations |
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| ID | Term |
|---|---|
| D000077487 | Pramipexole |
| ID | Term |
|---|---|
| D052160 | Benzothiazoles |
| D013844 | Thiazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
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Change in depression symptoms (total score on the MADRS). The range is 0-60, lower score indicating less general depressive symptoms. |
| baseline to week 10 |
| Snaith-Hamilton Anhedonia Pleasure Scale | Change in anhedonia symptoms (total score on the Snaith-Hamilton Anhedonia Pleasure Scale) score 0-1-2-3. Range 0-32. Higher score indicating more intense anhedonic symptoms. | baseline to week 10 |
| Generalized Anxiety Disorder-7 | Change in anxiety symptoms (total score on the the Generalized Anxiety Disorder-7 scale = GAD-7). Range 0-21. Higher score indicating more anxiety. | baseline to week 10 |
| Insomnia Severity Index | Change in insomnia symptoms (total score on the the Insomnia Severity Index scale = ISI). Range 0-28. Higher score indicating more insomnia symptoms. | baseline to week 10 |
| Fatigue Severity Scale | Change in fatigue symptoms (total score on the the Fatigue Severity scale = FSS). Range 9-63. Higher score indicating more fatigue. | baseline to week 10 |
| The Apathy Evaluation Scale | Change in apathy symptoms (total score on the the The Apathy Evaluation Scale = AES). Range 0-54. Higher score indicating more severe apathy. | baseline to week 10 |
| Change in Inflammatory Biomarkers | The investigators will measure blood levels of Interleukin-6 (IL-6), C-reactive protein (CRP), Tumor Necrosis Factor Alpha (TNF), and White Blood Cell count (WBC) 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 |
| Participation in fMRI With MID-task | fMRI = functional magnetic resonance tomography. Structural imaging, followed by resting-state functional imaging, diffusion tensor imaging and thereafter the MID (monetary incentive delay) task. | baseline to week 10 (and baseline data as potential predictor) |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
| Tobacco users | Number | Participants |
|
| hsCRP | Serum high sensitivity C-reactive peptide | Mean | Standard Deviation | mg/L |
|
| Concurrent pharmacological treatment | Ongoing psychoactive treatment at baseline | Number | Participants |
|
| ECT | Previously treated with electro-convulsive therapy | Count of Participants | Participants |
|
| Anxiety comorbidity | Anxiety disorder diagnosis at baseline | Count of Participants | Participants |
|
| Number of previous antidepressants | Median number of previously tried antidepressant treatments | Median | Full Range | Number of different antidepressants |
|
|
| Secondary | Response | Montgomery Åsberg Depression Rating Scale (MADRS). The range is 0-60, lower score indicating less general depressive symptoms. Response definition: reduction of at least 50% Remission definition: MADRS total score equal to or below 10 | Posted | Count of Participants | Participants | baseline to week 10 |
|
|
|
| Secondary | Montgomery Åsberg Depression Rating Scale (MADRS) Score | Change in depression symptoms (total score on the MADRS). The range is 0-60, lower score indicating less general depressive symptoms. | Posted | Mean | Standard Deviation | score on a scale | baseline to week 10 |
|
|
|
| Secondary | Snaith-Hamilton Anhedonia Pleasure Scale | Change in anhedonia symptoms (total score on the Snaith-Hamilton Anhedonia Pleasure Scale) score 0-1-2-3. Range 0-32. Higher score indicating more intense anhedonic symptoms. | Posted | Mean | Standard Deviation | score on a scale | baseline to week 10 |
|
|
|
| Secondary | Generalized Anxiety Disorder-7 | Change in anxiety symptoms (total score on the the Generalized Anxiety Disorder-7 scale = GAD-7). Range 0-21. Higher score indicating more anxiety. | Posted | Mean | Standard Deviation | score on a scale | baseline to week 10 |
|
|
|
| Secondary | Insomnia Severity Index | Change in insomnia symptoms (total score on the the Insomnia Severity Index scale = ISI). Range 0-28. Higher score indicating more insomnia symptoms. | Posted | Mean | Standard Deviation | score on a scale | baseline to week 10 |
|
|
|
| Secondary | Fatigue Severity Scale | Change in fatigue symptoms (total score on the the Fatigue Severity scale = FSS). Range 9-63. Higher score indicating more fatigue. | Posted | Mean | Standard Deviation | score on a scale | baseline to week 10 |
|
|
|
| Secondary | The Apathy Evaluation Scale | Change in apathy symptoms (total score on the the The Apathy Evaluation Scale = AES). Range 0-54. Higher score indicating more severe apathy. | Posted | Mean | Standard Deviation | score on a scale | baseline to week 10 |
|
|
|
| Secondary | Change in Inflammatory Biomarkers | The investigators will measure blood levels of Interleukin-6 (IL-6), C-reactive protein (CRP), Tumor Necrosis Factor Alpha (TNF), and White Blood Cell count (WBC) at baseline and at study completion. The investigators will test if baseline levels and treatment-associated change in inflammatory markers can predict treatment response | Posted | Mean | Standard Deviation | mg/L | baseline to week 10 |
|
|
|
| Secondary | Participation in fMRI With MID-task | fMRI = functional magnetic resonance tomography. Structural imaging, followed by resting-state functional imaging, diffusion tensor imaging and thereafter the MID (monetary incentive delay) task. | Posted | Count of Participants | Participants | baseline to week 10 (and baseline data as potential predictor) |
|
|
|
| 12 |
| 0 |
| 12 |
| 12 |
| 12 |
| Nausea | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Skin rashes | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Loss of appetite | Metabolism and nutrition disorders | Systematic Assessment |
|
| Vertigo | General disorders | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | Systematic Assessment |
|
| Agitation (mild) | Psychiatric disorders | Systematic Assessment |
|
| Overeating | Psychiatric disorders | Systematic Assessment |
|
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Mania | Psychiatric disorders | Systematic Assessment |
|
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| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 |
| Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |