Safety and Efficacy of Pramipexole Treatment in Resistant Obsessive-Compulsive Disorder (OCD) (OCD-RT)

Safety and Efficacy of Pramipexole Treatment in Resistant Obsessive-Compulsive Disorder (OCD): Pilot, Randomized and Controlled Clinical Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Drug: Pramipexole 0.088mg/tid; Drug: Pramipexole 0.18 mg/tid; Drug: Pramipexole 0.35 mg/tid

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mónica Gonçalves; Phone Number: +351 253 027 249; Email: 2ca@ccabraga.org
• Study Contact Backup: Name: Joana Reis; Phone Number: +351 253 027 249; Email: cro@ccabraga.org

Study Locations

• Portugal
  • Braga, Portugal, 4710-243
    • Recruiting
    • Clinical Academic Center - Braga (2CA-Braga)
    • Contact: Pedro Morgado, MD, PhD; Phone Number: +351253027249; Email: pedromorgado@med.uminho.pt
    • Contact: Pedro Morgado, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 (<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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pramipexole at a dose of 0.088 mg/tid; Treatment with antidepressant and pramipexole at a dose of 0.088 mg/tid (0.125 mg of salt)	Drug: Pramipexole 0.088mg/tid; Week 1 - Week 16 (end of treatment): Oral administration of 0.088 mg/tid dose of pramipexole (0.125 mg of salt).
Experimental: Pramipexole at a dose of 0.18 mg/tid; Treatment with antidepressant and pramipexole at a dose of 0.18 mg/tid (0.25 mg of salt)	Drug: Pramipexole 0.18 mg/tid; Week 1: oral administration of 0,088 mg/tid dose of pramipexole (0.125 mg salt). Week 2 -Week 16 (end of treatment): oral administration of 0.18 mg/tid dose of pramipexole (0.25 mg salt).
Experimental: Pramipexole at a dose of 0.35 mg/tid; Treatment with antidepressant and pramipexole at a dose of 0.35 mg/tid (0.50 mg of salt)	Drug: Pramipexole 0.35 mg/tid; Week 1: oral administration of 0,088 mg/tid dose of pramipexole (0.125 mg salt). Week 2: oral administration of a 0.18 mg/tid dose of pramipexole (0.25 mg salt). Week 3 - Week 16 (end of treatment): oral administration of a 0.35 mg/tid dose of pramipexole (0.50 mg salt).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between baseline and after treatment in Y-BOCS total score	The measurement of the difference in the total score of the Y-BOCS scale between baseline (before intervention with the investigational drug) and after intervention with the investigational drug, between the different groups treated with different doses of pramipexole. The Y-BOCS scale measures obsessions separately from compulsions and specifically measures the severity of symptoms of obsessive-compulsive disorder without being biased towards or against the type of content the obsessions or compulsions might present. The final scores range from 0 to 40, with higher scores indicating higher symptom severity. The scores indicate subclinic (0 - 7 points), mild (8 - 15 points), moderate (16 - 23 points), severe (24 - 31 points), and extreme severity (32 - 40 points).	Baseline and Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events observed	Number of adverse events observed (nonserious, serious not related to the investigational medicinal product, and serious related to the investigational medicinal product)	From Day 2 (after the first dose of the investigational drug) until Week 22 (end of study)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
OCI-R Total score	Obsessive-Compulsive Inventory-Revised (OCI-R) is a self-report instrument that assesses the symptoms of OCD during the last month through 18 statements that are related to everyday situations. The total score ranges from 0 to 72 points. Higher scores on this scale indicate higher severity of OCD symptoms.	Baseline, Day 1, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
Scores of the 4 subscales of the WHOQOL-bref	The Quality of Life Scale (WHOQOL-bref) is an instrument that assesses four conceptual domains of quality of life: material and physical well-being, relationships with other people, psychological well-being and environment. This self-report instrument, consisting of a brief sociodemographic questionnaire and 26 statements, quantifies global cognitive judgments of life satisfaction.	Baseline (before intervention), Week 16 (after intervention ), and Week 22 (end of study)
HAM-D Total score	Hamilton Depression Rating Scale (HAM-D) instrument to measure the psychic and somatic components of depression. From 0 - 7 the participant is considered asymptomatic, while a score equal to or greater than 20 indicates the presence of depressive symptoms. The higher the value, the greater the severity of the symptoms, ranging from moderate to severe.	Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
HAM-A Total score	Hamilton Anxiety Rating Scale (HAM-A) instrument to measure the psychic and somatic components of anxiety. The final scores indicate: mild anxiety (0 - 17 points), moderate anxiety (18 - 24 points) and potentially worrying levels of anxiety (25 - 30 points).	Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
PSS-10 Total score	Perceived Stress Scale (PSS-10) is a self-report questionnaire to assess perceived stress during the last month. The total score can vary between 0 and 40 points. A higher total score indicates higher levels of perceived stress.	Baseline, Day 1, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
SIQ total score	The Suicidal Ideation Questionnaire (SIQ) assesses thoughts and cognitions about suicide and death over the past month. Higher scores in the SIQ scale represent greater severity of suicidal ideation. The total score ranges from 0 to 180 points.	Baseline, Day 1, Day 7, Day 14, Day 21, Day 28, Week 8, Week 12, Week 16, Week 18 and Week 22
Neurobiological parameters - Cortical thickness	Anatomical sequence (Magnetization Prepared - RApid Gradient Echo) to assess cortical thickness	Baseline (before intervention) and Week 16 (after intervention with the investigational drug).
Neurobiological parameters - Functional connectivity	Functional sequences (Echo-planar imaging) at rest to assess functional connectivity of neural networks and static and dynamic connectivity	Baseline (before intervention) and Week 16 (after intervention with the investigational drug).
Neurobiological parameters - Brain activity	Functional sequences (Echo-planar imaging) during an emotional processing task to assess brain activation during emotional processing	Baseline (before intervention) and Week 16 (after intervention with the investigational drug).
Neurobiological parameters - Diffusion	Diffusion sequences (Diffusion Weighted Imaging) to measure mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD), in order to assess white matter integrity.	Baseline (before intervention) and Week 16 (after intervention with the investigational drug).
Biochemical parameters - Complete blood count	Blood samples will be collected to measure the complete blood count.	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Biochemical parameters - Cortisol	Blood samples will be collected to measure the cortisol.	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Biochemical parameters - ACTH	Blood samples will be collected to measure the adrenocorticotropic hormone (ACTH).	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Biochemical parameters - T4	Blood samples will be collected to measure the thyroxine (T4).	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Biochemical parameters - TSH	Blood samples will be collected to measure the thyroid stimulating hormone (TSH).	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Biochemical parameters - creatinine	Blood samples will be collected to measure the creatinine.	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Biochemical parameters - glucose	Blood samples will be collected to measure the glucose.	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Biochemical parameters - glycated hemoglobin	Blood samples will be collected to measure the glycated hemoglobin.	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)
Biochemical parameters - Prolactin	Blood samples will be collected to measure the prolactin.	Baseline (before intervention ), Week 16 (after intervention) and Week 22 (end of the study)

Collaborators and Investigators

• Sponsor: Clinical Academic Center (2CA-Braga)
• Investigators: Principal Investigator: Pedro Morgado, MD, PhD, 2CA-Braga

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2024
• Primary Completion (Estimated): August 20, 2028
• Study Completion (Estimated): August 20, 2028

Study Registration Dates

• First Submitted: September 4, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Antioxidants; Protective Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agonists; Pramipexole; Dexpramipexole
• Other Study ID Numbers: OCD_rt; 2024-511085-37-00 (Ctis)

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