CTC-501 for Depression

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chase Therapeutics Corporation

Must not be taking: Pramipexole, Ondansetron, MAOI, others

Disqualifiers: Pregnancy, Renal dysfunction, Substance abuse, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate a new treatment, CTC-501, for individuals with major depressive disorder (MDD), characterized by persistent sadness and loss of interest. Participants will receive either the experimental medication or a placebo (a pill with no active ingredients) to compare effects. Ideal candidates are those diagnosed with MDD who are not currently on antidepressants or are willing to pause their current medication. The study seeks to uncover more effective ways to manage depression symptoms. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of potentially more effective depression treatments.

Will I have to stop taking my current medications?

If you are currently on antidepressants, you may need to stop taking them and go through a washout period (time without taking certain medications) before joining the trial. Some antidepressants, like fluoxetine, may require a longer washout period of more than 2 weeks.

Is there any evidence suggesting that CTC-501 is likely to be safe for humans?

Research has shown that the treatment CTC-501, which combines pramipexole with ondansetron, has been studied for safety in people with depression. In other studies, pramipexole was tested on patients with depression and was generally well-tolerated. However, some common side effects, such as nausea, headache, dizziness, and sleep problems, were noted. These side effects are typical and manageable for many patients.

Previous research compared pramipexole to other depression treatments and found a similar safety profile. While pramipexole is not yet approved specifically for depression, its use in other conditions provides some insight into its safety. This trial aims to further understand the safety and effectiveness of CTC-501 for treating major depressive disorder. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for depression, which often include SSRIs, SNRIs, and psychotherapy, CTC-501 is unique because it combines pramipexole IR with ondansetron. Pramipexole, typically used for Parkinson’s disease, acts on dopamine D2/D3 receptors, offering an innovative approach by potentially targeting dopamine pathways that aren't the primary focus of most antidepressants. Additionally, the inclusion of ondansetron, a medication usually used to prevent nausea, could help mitigate some side effects, making this combination particularly intriguing for researchers. This dual-action approach might provide faster or more effective relief for patients who haven't responded to traditional therapies.

What evidence suggests that CTC-501 might be an effective treatment for depression?

Research has shown that CTC-501, which contains pramipexole, might help improve depression symptoms. In this trial, participants will receive either CTC-501 with ondansetron or a placebo. Some studies found that CTC-501 reduced symptoms more effectively than a placebo. However, other studies found that pramipexole alone did not significantly help people with major depressive disorder (MDD). Despite these mixed results, evidence suggests that pramipexole could benefit those with treatment-resistant depression. While there is potential, researchers continue to study how well CTC-501 works for MDD. ^{1 3 5 6 7}

Who Is on the Research Team?

Mark Leibowitz, MD

Principal Investigator

Collaborative Neuroscience Network

Are You a Good Fit for This Trial?

This study is for men and women aged 18-65 with major depressive disorder (MDD), who score above a certain level on the HAM-D depression scale. Participants must not be on antidepressants or agree to stop them before starting the trial, and can't start new psychotherapies during the trial. Pregnant or breastfeeding women, those with significant liver or kidney issues, drug abuse history, serious suicidal risk, or certain other health conditions are excluded.

Inclusion Criteria

I have been diagnosed with major depressive disorder.

I have been diagnosed with major depression without psychosis.

I agree not to start new mental health therapies during the trial, but can continue if already started 3+ months ago.

Exclusion Criteria

Lifetime history of certain mental health disorders

History of serious suicidal attempt or tendencies

My kidney and liver functions are within specific limits.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Titration

Participants receive pramipexole titrated up to the first intolerable dose or maximum allowed dose

1 week

Daily visits (in-person) until FID or Day 8

Maintenance

Participants continue treatment with pramipexole at maximum tolerated dose or placebo for 8 weeks

8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CTC-501

Trial Overview The clinical trial is testing CTC-501 in patients with MDD. It's a Phase 2a study where participants will either receive this experimental medication or a placebo without knowing which one they're getting (single-blind). The goal is to see if CTC-501 helps improve symptoms of depression compared to no active treatment.

How Is the Trial Designed?

Group I: treatment Experimental Treatment 1 Intervention

CTC-501 (pramipexole IR, given with ondansetron) given orally twice daily

Group II: placebo Placebo Group 1 Intervention

generic placebo tablets given orally twice daily

Who Is Running the Clinical Trial?

Chase Therapeutics Corporation

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

A review of 10 clinical trials on esketamine for resistant depression found that 90% of the trials had low-quality reporting of adverse events (AEs), indicating significant gaps in safety data.

The study revealed that 41.5% of serious AEs and 39% of non-serious AEs were not reported in published articles, particularly psychiatric and cardiovascular events, suggesting that the assessment of esketamine's risk-benefit balance may be inaccurate due to incomplete harm reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of harms in clinical trials of esketamine in depression: a systematic review. Taillefer de Laportalière, T., Jullien, A., Yrondi, A., et al.[2023]

In a study involving 97 participants with treatment-resistant depression, ketamine infusions showed a 67% response rate, indicating significant antidepressant effects.

The treatment was found to be safe and well-tolerated, with only a 3.1% attrition rate and no cases of persistent adverse effects, although some participants experienced temporary side effects like drowsiness and dissociation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine safety and tolerability in clinical trials for treatment-resistant depression. Wan, LB., Levitch, CF., Perez, AM., et al.[2022]

The REMIT tool, a brief 5-item questionnaire, has been validated as an effective measure for assessing and predicting improvement in depression among 294 primary care patients, showing strong correlations with mental health metrics.

With a minimally important difference (MID) of about 2 points, REMIT was found to be as effective, if not better, than the PHQ-9 in predicting depression improvement over a 6-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing depression improvement with the remission evaluation and mood inventory tool (REMIT). Bushey, MA., Kroenke, K., Baye, F., et al.[2020]

Esketamine nasal spray combined with an oral antidepressant significantly improves treatment outcomes for patients with treatment-resistant depression, with 5-21 more patients achieving remission and 14-17 more responding compared to those on a placebo during induction therapy.

In maintenance therapy, esketamine reduces the risk of relapse by 19-32 patients, while the incidence of serious adverse events remains low, indicating a favorable benefit-risk profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment-Resistant Depression. Katz, EG., Hough, D., Doherty, T., et al.[2021]

In two large trials involving adults with major depressive disorder who did not respond adequately to standard antidepressants, adjunctive treatment with aripiprazole (2-20 mg/day) significantly improved depression scores compared to placebo, starting from 1-2 weeks into treatment.

Aripiprazole was generally well tolerated, with most side effects being mild to moderate, and it also led to higher rates of response and remission compared to placebo, indicating its efficacy as an adjunctive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole: in major depressive disorder. Weber, J., Lyseng-Williamson, KA., Scott, LJ.[2021]

Ketamine shows promise as a treatment for treatment-resistant depression (TRD), but its use can lead to common adverse events, which are usually temporary.

A case of apnea during a slow sub-anesthetic infusion of ketamine highlights a rare but serious potential side effect, emphasizing the need for careful monitoring and management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. Gómez-Revuelta, M., Fernández-Rodríguez, M., Boada-Antón, L., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11428619/

Comparative Short- and Long-Term Effectiveness ... A meta-analysis of 18 randomized controlled trials showed that pramipexole improves depressive symptoms in patients with Parkinson's disease [ ...

2. thelancet.com thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00194-4/fulltext

Pramipexole augmentation for the acute phase of treatment ... Meta-analyses by Tundo and colleagues found no significant effect of pramipexole on efficacy outcomes in patients with major depressive disorder ...

3. secure.medicalletter.org secure.medicalletter.org/TML-article-1739c

Adjunctive Pramipexole for Treatment-Resistant Depression Data from observational studies suggest that pramipexole can be effective in patients with bipolar depression,7 but a recently published ...

4. investors.altoneuroscience.com investors.altoneuroscience.com/news/news-details/2025/Alto-Neuroscience-Announces-Acquisition-of-Novel-Dopamine-Agonist-Combination-Product-Candidate-Adding-Late-Stage-Readout-in-Treatment-Resistant-Depression-Within-Current-Cash-Runway/default.aspx

News Details CTC-501 demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo on depression symptoms ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00231959

Effectiveness of Pramipexole for Treatment-Resistant ... This study will evaluate the effectiveness of pramipexole in treating depression in individuals that have not responded to other medications.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03642964

A Study in Patients With Major Depressive Disorder This is a Phase 2a, placebo-controlled, single-blind study in up to 24 patients with major depressive disorder (MDD). Subjects will sign consent form prior ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725015290

Efficacy and tolerability of pramipexole versus ... This meta-analysis aims to directly compare the safety and efficacy of pramipexole and antidepressants for depression in PD patients.