Clinical trial NCT06611592: Safety and Efficacy of Pramipexole Treatment in Resistant Obsessive-Compulsive Disorder (OCD)
Official title: Safety and Efficacy of Pramipexole Treatment in Resistant Obsessive-Compulsive Disorder (OCD): Pilot, Randomized and Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Obsessive-Compulsive Disorder
Lead sponsor: Clinical Academic Center (2CA-Braga)
Sponsor class: OTHER
First posted: 2024-09-25
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The most common and effective treatment for OCD is pharmacological therapy that includes selective serotonin reuptake inhibitors (SSRIs) antidepressants and, in the case of patients resistant to this approach, a combination with antipsychotics. Risperidone and aripiprazole are atypical antipsychotics that act on dopamine (D2) and serotonin receptors. Studies have shown that these drugs are effective in boosting SSRIs for the treatment of OCD in resistant patients.

Currently a high percentage of people diagnosed with OCD do not respond to the existing treatments. Pramipexole is a dopaminergic receptor agonist that specifically binds to dopamine D2 and D3 receptors, having demonstrated benefit in resistant depression.

The aim of this clinical trial is to explore how pramipexole can act in the treatment of OCD in resistant patients, evaluating its safety and efficacy.

Detailed description: Phase 2 clinical trial, randomized, with three-parallel-groups, lasting 26 weeks (screening phase, 4 weeks + treatment phase, 16 weeks + follow-up phase, 6 weeks), whose primary objective is to evaluate the effectiveness of using pramipexole as a strategy for boosting SSRIs, in three different doses, in treatment of resistant OCD.

The main endpoint is the measurement of the difference in the total score of the Y-BOCS scale between baseline (V1; before intervention with the investigational drug) and week 16 (V9; after intervention with the investigational drug), between the different groups treated with different doses of pramipexole.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 64 years;
2. European Portuguese as mother tongue;
3. Patients diagnosed with OCD, regardless of subtype, according to DSM-5 and/or ICD-10 criteria;
4. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score ≥ 16;
5. Patients resistant to the first-line treatment for OCD:

5.1 Patients who do not respond to treatment with at least two selective serotonin reuptake inhibitor antidepressants (SSRIs) at the maximum tolerated therapeutic dose during at least 12 weeks, i.e. patients in whom there is no reduction in the Y-BOCS score by 25% relative to the score obtained before starting treatment with SSRIs.

5.2 Patients who do not respond to treatment with risperidone or aripiprazole as potentiation of the SSRIs at the maximum tolerated therapeutic dose during at least 12 weeks, i.e. patients in whom there is no reduction in the Y-BOCS score by 25% relative to the score obtained before starting treatment with the antipsychotic or patients in whom the Y-BOCS score is kept ≥ 16 after the treatment with the antipsychotic.

Exclusion Criteria:

1. Patients with current or anterior history of psychotic illness (schizophrenia, delusions, among others);
2. Patients with bipolar disorder;
3. Patients with tick disorder;
4. Patients with borderline personality disorder;
5. Patients with social anxiety disorder;
6. Patients with current or anterior history of dietary behavior disorders (at least in the last 6 months);
7. Patients with a history of neurological disease or traumatic brain injury;
8. Patients with history of alcohol abuse or illicit substances (at least in the last 6 months);
9. Patients who are passing or have passed in the last 6 months by a major depressive episode;
10. Patients that undergo deep brain stimulation;
11. Presence of sensory deficits impeding participation in clinical study;
12. Pregnant or in breastfeeding period;
13. Patients who are doing or have done psychotherapy in the last 6 months;
14. Patients doing medication or receiving prohibited treatments;
15. Patients with allergy to pramipexole or any of the excipients;
16. Patients with creatinine clearance ≤ 50 ml/min (calculated by Cockcroft-Gault formula);
17. Patients with NYHA III or IV heart failure or any other severe cardiovascular disease;
18. Hypotension (\&lt;90/60 mmHg) sitting position and hypotension orthostatic (drop in systolic AT ≥20 mmHg or diastolic AT ≥10 mmHg after 2-3 minutes of orthostatism) at the screening;
19. Patients with contraindication to perform MRI cannot participate in the assessment of the exploratory endpoint (i.e., other pre-specified outcomes).

Primary outcomes:
measure: Difference between baseline and after treatment in Y-BOCS total score
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Number of adverse events observed
timeFrame: From Day 2 (after the first dose of the investigational drug) until Week 22 (end of study)
Other outcomes:
measure: OCI-R Total score
timeFrame: Baseline, Day 1, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
measure: Scores of the 4 subscales of the WHOQOL-bref
timeFrame: Baseline (before intervention), Week 16 (after intervention ), and Week 22 (end of study)
measure: HAM-D Total score
timeFrame: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
measure: HAM-A Total score
timeFrame: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
measure: PSS-10 Total score
timeFrame: Baseline, Day 1, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
measure: SIQ total score
timeFrame: Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
measure: Neurobiological parameters - Cortical thickness
timeFrame: Baseline (before intervention) and Week 16 (after intervention with the investigational drug).
measure: Neurobiological parameters - Functional connectivity
timeFrame: Baseline (before intervention) and Week 16 (after intervention with the investigational drug).
measure: Neurobiological parameters - Brain activity
timeFrame: Baseline (before intervention) and Week 16 (after intervention with the investigational drug).
measure: Neurobiological parameters - Diffusion
timeFrame: Baseline (before intervention) and Week 16 (after intervention with the investigational drug).
measure: Biochemical parameters - Complete blood count
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
measure: Biochemical parameters - Cortisol
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
measure: Biochemical parameters - ACTH
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
measure: Biochemical parameters - T4
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
measure: Biochemical parameters - TSH
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
measure: Biochemical parameters - creatinine
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
measure: Biochemical parameters - glucose
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
measure: Biochemical parameters - glycated hemoglobin
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
measure: Biochemical parameters - Prolactin
timeFrame: Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Locations:
city: Braga
country: Portugal
facility: Clinical Academic Center - Braga (2CA-Braga)
Study officials:
affiliation: 2CA-Braga
name: Pedro Morgado, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: