Adjuvant treatment with Pramipexole for anhedonia symptoms in depression - PRIME-PRAXOL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

16 Oct 2022 → ongoing

Decision date (initial)

2024-04-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512495-35-00

EudraCT number

2022-001563-26

ClinicalTrials.gov

NCT05355337

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Therapy, Safety, Efficacy

Will treatment with pramipexole at the highest possible dosage (without intolerable adverse reactions, max 3.15 mg base) reduce anhedonia symptoms over a nine-week period compared to placebo treatment?

Secondary objectives 8

1. Will treatment with pramipexole at the highest possible dose (without intolerable adverse reactions, max 3.15 mg base) reduce depression symptoms (Bech-6 scale) over a nine-week period?
2. Will treatment with pramipexole at the highest possible dose (without intolerable adverse reactions, max 3.15 mg base) increase daily physical activity, reduce stress, and improve sleep quality as recorded by activity meters over a nine-week period?
3. Will treatment with pramipexole at the highest possible dose (without intolerable adverse reactions, max 3.15 mg base) reduce psychological symptoms as measured by the DARS-SV-MOD, MADRS, AES, Insomnia Severity Scale, BBQ and GAD-7 rating scales over a nine-week period?
4. Will treatment with pramipexole at the highest possible dose (without intolerable adverse reactions, max 3.15 mg base) increase the activity of the ventral striatum in the context of the MID task at fMRI?
5. Can inflammatory and dopamine turnover markers in blood and CSF and activity and connectivity in the ventral striatum during MID task predict the treatment response of pramipexole?
6. Is pramipexole a safe and tolerable treatment in anhedonic depression?
7. Is the cognitive functional profile related to state (symptom pressure/anhedonia) or scar/trait (duration/vulnerability) after treatment with pramipexole?
8. Will treatment with pramipexole at the highest possible dose (without intolerable adverse reactions, max 3.15 mg base) improve the performance of PRT over a nine-week period?

Conditions and MedDRA coding

Major depression

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥18 years ≤75 years.
2. Diagnosis of unipolar depressive episode, bipolar disorder in depressive phase, or dysthymia.
3. Anhedonia symptoms: 3 or 4 points on ≥ 3 items of the Snaith-Hamilton Pleasure Scale (SHAPS-C).
4. Ongoing treatment with at least one antidepressant or mood stabilizing medication ≥ 4 weeks.
5. Has tried an antidepressant at a therapeutic dose but not achieved remission (refractory stage 1 depression).
6. The research subject has given informed consent to participate in the study.

Exclusion criteria 15

1. Pregnancy, breastfeeding or planned pregnancy (if female).
2. High suicide risk according to the overall clinical assessment of the research physician.
3. Ongoing substance abuse (within 6 months).
4. Diagnosis of current psychosis.
5. Known diagnosis of Emotionally Unstable Personality Disorder.
6. Treatment under LPT.
7. History of or a strong clinical suspicion of impulse control disorder (including current bingeeating disorder) or a current ADHD diagnosis with hyperactivity.
8. Diagnosis of intellectual disability, dementia, or other circumstance that makes it difficult to understand the meaning of participating in the trial and give informed consent.
9. Diagnosis of renal failure (eGFR < 50 ml/min/1,73 m2) or severe cardiovascular disease (specifically symptomatic heart failure NYHA Class II or higher).
10. Recently started psychotherapy (within 6 weeks) or planning to start such treatment during participation in the trial.
11. Ongoing or planned ECT, ketamine or rTMS treatment, excluding maintenance ECT, ketamine or rTMS (Maintenance treatment is defined as the use of ECT/ketamine/rTMS for a period exceeding 3 months after a series of ECT/ketamine/rTMS treatment in order to prevent the onset of a new episode).
12. Other medical conditions or other concomitant drug treatment which, 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, bariatric surgery with a known impact on absorption of extended-release tablets.
13. Known or suspected allergy to any active substance or excipient in the medicinal product included in the trial.
14. Participation in other treatment studies.
15. Other reason, as assessed by the investigator, that prevents the research subject's participation, such as the risk that the research subject is unable to complete the trial (non-compliance).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. SHAPS-C (total SHAPS-C scores at baseline, week 3, week 6 and week 9).

Secondary endpoints 8

1. HDRS6 scores (subscale of HDRS-17).
2. Number of steps/day, movement pattern distribution over the day, walking distance, time spent in light, moderate and intense physical activity, resting heart rate, blood oxygen saturation, heart rate variability (stress scores), sleep latency, sleep awakening, wakefulness, time in deep sleep, sleep efficiency. All variables are measured using activity meters.
3. Total scores of DARS-SV-MOD, MADRS, AES, Insomnia Severity Scale GAD-7 and BBQ.
4. BOLD activity in the nucleus accumbens during fMRI (MID task).
5. Biomarkers related to dopamine and inflammation, measured in blood and CSF. BOLD activity in the nucleus accumbens during MID task fMRI and connectivity during diffusion tensor imaging.
6. Gathering of adverse events.
7. Neuropsychological test battery consisting of WAIS-IV, RBANS, D-KEFS, CPT-3 and cognitive self-assessment PDQ-5.
8. The test Probabilistic Reward Task (PRT)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Daniel Lindqvist

Public contact point

Organisation

Region Skane

Contact name

Daniel Lindqvist

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications