Pramipexole vs Placebo Treatment in Bipolar Disorder With Anhedonic Depression

Phase 3Not Yet RecruitingNCT07664852

Daniel Lindqvist126 enrolled

Overview

Among psychiatric disorders, bipolar disorder stands out due to its alarmingly high suicide rates. This condition presents unique management challenges, especially during its depressive phase, which carries the highest risk of suicide. B-HAPPI is an academic randomized controlled trial to evaluate a new medication for bipolar depression. It will investigate the efficacy and safety of pramipexole, a potent dopamine agonist that has demonstrated significant effectiveness in bipolar disorder in preliminary studies, showing large effect sizes. * Population: 126 patients with bipolar depression * Intervention: Pramipexole added to ongoing treatment with mood stabilizer, flexible dosing - target dose 2.1 mg/day * Control: Add-on identical placebo * Outcomes: Primary outcome is change in anhedonia symptoms between baseline and 6 weeks of intervention. Key secondary outcomes include (for example) general depression symptoms and safety measures. There will be a 15 weeks open label follow up. If shown to be effective and safe, this intervention could become a key treatment option for bipolar depression, reducing suffering and potentially lowering suicide risk.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

126

Conditions

Bipolar Disorder (BD)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * The participant has given their written consent to participate in the trial. * For WOCBP, adequate contraception should be used (see section 9.6) and a negative pregnancy test is (u-hCG) required. WOCBP: For the purpose of this protocol, a woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. * Age ≥18 years ≤80 years. * Diagnosis of bipolar disorder type I or II as verified by ICD-11. * Ongoing depressive state according to ICD-11 (at least 2 weeks, maximum 18 months). * Significant anhedonia, defined as 3 or 4 points on ≥3 items on the SHAPS self-rating scale * Minimum score on the MADRS expert rating scale ≥ 20 * Ongoing treatment with at least one mood stabilising agent (with sufficient antimanic protection as determined by clinical judgment). If treatment with lithium is ongoing, serum levels must be within the reference range of 0.4-0.9. The latest concentration measurement should be within one month before treatment initiation. If treatment is ongoing with a mood stabilising anticonvulsant or an antipsychotic, any dose adjustments made within 4 weeks prior to study start must be reported. Mood-stabilising anticonvulsants and antipsychotics must not be newly initiated within 4 weeks prior to study start. If treatment with antidepressants is ongoing the dose must have been stable for at least 4 weeks. Exclusion Criteria: * Pregnancy, breastfeeding or planned pregnancy (if female). See also section 8.6 below for clarification. * Meets criteria for a mixed episode according to ICD-11. * High suicide risk according to the overall clinical assessment of the research physician. * Ongoing substance abuse (within 6 months). * Ongoing psychotic symptoms. * Prior diagnosis of schizophrenia or schizoaffective disorder. * Clinical presentation is primarily attributable to a personality disorder. * Subject to compulsory psychiatric care (LPT). * History of, or strong clinical suspicion of, impulse control disorder (including current binge-eating disorder). A diagnosis of ADHD is not, in itself, an exclusion criterion; however, participants will be excluded if the clinical presentation is primarily characterised by impulse control-related symptoms. * Diagnosis of intellectual disability, dementia, cognitive impairment, or other conditions (including those related to the depressive disorder itself) that, in the judgment of the study physician, may substantially impair the participant's ability to understand the study and provide informed consent. * Diagnosis of renal failure (eGFR \<50 ml/min/1.73m2) or severe cardiovascular disease (specifically symptomatic heart failure \>Class II New York Heart Association (NYHA)). * Recently started psychotherapy (within 6 weeks) or planning to start such treatment during participation in the trial. Psychoeducational treatment, which is standard care at bipolar units, is not an exclusion criterion. * Ongoing treatment with ECT, ketamine or rTMS. * Other medical conditions, other ongoing interventions or other concomitant drug treatment (see section 7.3) that, in the opinion of the investigators, may affect the evaluability of the trial or conditions that increase trial risk. For example: Parkinson's disease, hepatic insufficiency, ongoing cancer not in remission for more than one year. * Known or suspected allergy to any active substance or excipient in the medicinal product included in the trial. * Participation in other treatment studies. * Other reason, as assessed by the investigator, that prevents the research participant's participation, such as the risk that the research participant is unable to complete the trial (non-compliance).

Outcomes

Primary Outcomes

Change in Snaith-Hamilton Pleasure Scale (SHAPS) self-reported total score after 6 weeks of treatment compared to baseline

14 items rated from points with 1 to 4. Higher scores equal more severe anhedonia. Score range: 14-56.

Time frame: Between baseline visit and week 6

Secondary Outcomes

Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6 and week 21

10 items are rated with a score of 0 to 6 (total score: 0 to 60). A higher MADRS score indicates more severe depression. Cut-off points: 0 to 6: normal/symptom-free, 7 to 19: mild depression, 20 to 34: moderate depression 35 to 60: severe depression.

Time frame: Between baseline visit and week 21

Change in sedentary behaviour (SED) between baseline, week 6 and week 21

Parameter is part of determining physical activity measured by wearable activity meters

Time frame: Between baseline and week 21

Change in light physical activity (LPA) between baseline, week 6 and week 21

Parameter is part of determining physical activity measured by wearable activity meters

Time frame: Between baseline and week 21

Change in moderate- to vigorous physical activity (MVPA) between baseline, week 6 and week 21

Parameter is part of determining physical activity measured by wearable activity meters

Time frame: Between baseline and week 21

Change in Dimensional Anhedonia Rating Scale (DARS) from baseline to week 6 and 21

Scale consists of 17 items divided into four subdomains (Hobbies, Food/Drinks, Social Activities and Sensory Experiences). Each item is scored on a 5-point Likert scale ranging from 1 to 5. Higher score indicates greater ability to experience pleasure representing less anhedonia. Score range: 17 to 85.

Time frame: Between baseline visit and week 21

Change in Apathy Evaluation Scale (AES) from baseline to week 6 and 21

Scale consists of 18 items designed to measure aspects like goal-directed behavior, interest, and emotional responsiveness. Each question is scored on a Likert scale from 1 to 4, resulting in a total score ranging from 18 to 72, where higher scores indicate greater apathy.

Time frame: Between baseline visit and week 21

Change in Clinical Global Impression - Severity (CGI-S) between baseline, week 6 and 21

7-point scale that measures overall severity of a patient's mental illness with higher scores indicating more severe illness. Score range: 1 to 7.

Time frame: Between baseline and week 21

Change in EuroQol - Five dimensions - Five levels (EQ-5D-5L) between baseline, week 6 and 21

Patient evaluates their health across five core dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, Anxiety/Depression. For each dimension, the patient selects one of five severity levels that best describes their state: 1: No problems, 2: Slight problems, 3: Moderate problems, 4: Severe problems, 5: Extreme problems. These responses are combined into a 5-digit number (e.g., "11121" indicates no problems across the board except for slight pain/discomfort). This score is then converted into a total index value using country-specific population value sets. In addition, the patient rates their overall health on a vertical visual analogue scale that looks like a thermometer. 0: The worst health you can imagine vs 100: The best health you can imagine.

Time frame: Between baseline and week 21

Systematic registration of adverse events, especially (hypo)mania and impulse control related symptoms: Young Mania Rating Scale (YMRS)

The YMRS evaluates symptoms over the preceding 48 hours using an 11-item questionnaire: Elevated mood, increased motor activity, sleep patterns, sexual interest, irritability, speech, language-thought disorder, thought content, aggressive behavior, appearance, and insight. Scoring Weights: Seven items are rated on a severity scale of 0 to 4. Four core items are double-weighted (scored 0 to 8) to reflect their clinical significance: irritability, speech, thought content, and disruptive/aggressive behavior. Total scores range from 0 to 60, with higher numbers indicating more severe mania. ≤ 12: Typically indicates remission of manic symptoms.≥ 20: Generally corresponds to moderate-to-severe mania.

Time frame: Between baseline visit and week 21

Systematic registration of adverse events, especially (hypo)mania and impulse control related symptoms: Modified Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (M-QUIP-RS)

The scale is designed to evaluate seven primary impulse and compulsive behaviors: Compulsive gambling, Excessive buying/shopping, Binge-eating, Hypersexuality, Punding (intense fascination with repetitive handling or sorting of ordinary objects), Hobbyism (performing a hobby or task to an excessive degree), Dopamine Dysregulation Syndrome (DDS). The questionnaire features 4 questions for each of the 7 subdomains. Scoring: Patients or caregivers rate the severity of behaviors over the past month using a 5-point Likert scale (0 to 4). Total Score: Individual subscales range from 0 to 16, with a total overall score scaling up to 112.

Time frame: Between baseline visit and week 21

Systematic registration of adverse events, especially (hypo)mania and impulse control related symptoms: Modified Problem Gambling Severity Index (M-PGSI)

9-item questionnaire using a 4-point scale for each question: 0 (never) to 3 (almost always). The scores are totaled to produce a final result between 0 and 27: Score of 0: Non-problem gambling. You may gamble, but you do not report experiencing adverse consequences. Score of 1 to 2: Low-risk. You are unlikely to experience adverse consequences but may be at risk if heavily involved. Score of 3 to 7: Moderate-risk. You may have experienced some negative consequences and show signs of risky habits. Score of 8 or higher: Problem gambling. You are likely to experience severe adverse consequences and may have lost control of your behavior.

Time frame: Between baseline visit and week 21

Systematic registration of adverse events, especially (hypo)mania and impulse control related symptoms: Alcohol Use Disorders Identification Test (AUDIT)

10-question screening tool to assess alcohol consumption, drinking behaviors, and alcohol-related problems. Core Domains: Frequency of drinking, typical intake, binge drinking, loss of control, and guilt. Scale of 0 to 4 fro each item depending on frequency: 0 = Never, 1 = Less often than once a month, 2 = Every month, 3 = Every week, 4 = Daily or almost every day. Scoring: Scores range from 0 to 40. A score of 8+ typically indicates hazardous or harmful consumption.

Time frame: Between baseline visit and week 21

Systematic registration of adverse events, especially (hypo)mania and impulse control related symptoms: Drug Use Disorders Identification Test (DUDIT)

11-item self-report questionnaire designed to screen for drug-related problems, substance abuse, and dependence. Respondents answer the 11 questions using a scale of 0 to 4 depending on frequency: 0 = Never, 1 = Less often than once a month, 2 = Every month, 3 = Every week, 4 = Daily or almost every day. The 11 Items: The questionnaire includes 11 items covering frequency of drug use, consumption habits, inability to control usage, neglect of responsibilities, and physical/psychological consequences. 0 to 44 points in total, uses gender-specific cut-offs to determine risk levels, where scores of 6+ (women) or 8+ (men) often indicate potential dependence.

Time frame: Between baseline visit and week 21

Pramipexole vs Placebo Treatment in Bipolar Disorder With Anhedonic Depression

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts