Liafensine for Treatment Resistant Depression

(ENLIGHTEN Trial)

Recruiting at 41 trial locations

Overseen By Vineela Mallireddy

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: Denovo Biopharma LLC

Must not be taking: Antidepressants, ADHD medications

Disqualifiers: Psychotic disorders, Bipolar, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for people with depression who haven't responded to other treatments. The study will compare the new treatment to see if it helps improve their symptoms. Psilocybin-assisted therapy may be a new treatment for major depressive disorder (MDD), with encouraging data from pilot trials.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking your current antidepressant medications at least 5 half-lives before the trial starts. For fluoxetine, a longer washout period (time without taking the medication) of 3 to 4 weeks is required, depending on the dose.

What data supports the effectiveness of the drug Liafensine for depression?

The research on nomifensine, a similar drug, shows it was effective in treating certain types of depression, like anxious and suicidal depression, compared to a placebo. This suggests that Liafensine might also be effective for these subtypes of depression. ^{1 2 3 4 5}

Is Liafensine safe for humans?

The safety of Liafensine, also known as nomifensine, has been studied in various trials. It is generally well-tolerated with minimal side effects like sleep disturbance, restlessness, and nausea. It does not affect heart health or cause serious issues in overdose, and it has a favorable safety profile compared to other antidepressants. ^{6 7 8 9 10}

How is the drug Liafensine different from other depression treatments?

Liafensine is unique because it is being studied specifically for its effects on depression, potentially offering a new mechanism of action or formulation compared to existing antidepressants. Unlike standard treatments, this trial also includes a placebo group to better understand its effectiveness. ^{1 2 6 7 11}

Eligibility Criteria

This trial is for individuals with treatment-resistant Major Depressive Disorder, specifically those with the DGM4 genotype who have tried at least two antidepressants without success in the past 5 years. Men must comply with pregnancy prevention measures. People currently responding well to treatments, with substance abuse issues, significant health abnormalities, or recent cancer history (except certain skin cancers) cannot participate.

Inclusion Criteria

Have you been diagnosed with Major Depressive Disorder?

You have taken two or more different antidepressants within the past 5 years that felt ineffective.

You are currently experiencing depression.

Exclusion Criteria

You have previously taken part in a study involving the drug liafensine.

You have a medical condition that could interfere with how your body processes liafensine.

You have had cancer within the past two years, except for non-spreading skin cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Liafensine 1mg, Liafensine 2mg, or placebo in a randomized, double-blind manner

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Liafensine
• Placebo

Trial Overview The study tests Liafensine's effectiveness and safety against a placebo in patients with treatment-resistant depression. It's a Phase 2b trial involving about 180 participants who are randomly assigned to receive either Liafensine or a placebo without knowing which one they're getting.

Participant Groups

Group I: Liafensine 2mg Experimental Treatment 1 Intervention

Group II: Liafensine 1mg Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Denovo Biopharma LLC

Lead Sponsor

Trials

19

Recruited

3,200+

Findings from Research

A prediction model was developed using individual patient data from 1493 participants in four clinical trials to estimate the likelihood of responding to placebo in antidepressant trials, with a focus on variables like age and bodily symptoms.

The model showed good calibration and discrimination, indicating it can help identify individuals more likely to respond to placebo, which is crucial for understanding the effects of antidepressants in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of a prediction model for the probability of responding to placebo in antidepressant trials: a pooled analysis of individual patient data. Shinohara, K., Tanaka, S., Imai, H., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Development and validation of a prediction model for the probability of responding to placebo in antidepressant trials: a pooled analysis of individual patient data. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Pretreatment neurophysiological and clinical characteristics of placebo responders in treatment trials for major depression. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of nomifensine in different depressive syndromes. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Use of placebo control groups in evaluating efficacy of treatment of unipolar major depression. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Is drug-placebo difference in short-term antidepressant drug trials on unipolar major depression much greater than previously believed? [2009]

6. United States pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to antidepressant therapy. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of the efficacy and safety of lisdexamfetamine dimesylate as augmentation therapy in adults with residual symptoms of major depressive disorder after treatment with escitalopram. [2022]

8. Belgium pubmed.ncbi.nlm.nih.gov

[Study of nomifensine in the treatment of depressive states (author's transl)]. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

A review of the clinical safety and tolerability of nomifensine. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Double-blind comparison of the efficacy and safety of nomifensine maleate vs. placebo in depressed outpatients. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Open-Label placebo for the treatment of unipolar depression: Results from a randomized controlled trial. [2021]