Apimostinel + Cognitive Training for Depression

Overseen By Rebecca B Price, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Rebecca Price

Must not be taking: MAOIs, NMDA/AMPA drugs, others

Disqualifiers: Bipolar, Psychotic, Autism, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating depression by combining a potential new medication, apimostinel, with cognitive training exercises. Apimostinel may work quickly and with few side effects, while cognitive training aims to prolong the antidepressant effects. The trial will test apimostinel against a placebo (a substance with no therapeutic effect) and compare the effects with and without cognitive training. Individuals with major depressive disorder who have experienced significant symptoms and struggle with self-esteem may be a good fit for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to the development of potentially effective therapies.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as Monoamine Oxidase Inhibitors (MAOIs) at least 28 days before starting the trial, and medications affecting specific brain receptors like NMDA or AMPA. If you're on any of these, you may need to stop them before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that apimostinel is a promising new antidepressant with few side effects. Studies have found that it quickly eases depression symptoms. So far, people have tolerated apimostinel well. Safety data from earlier trials suggest no major concerns about its short-term use.

Cognitive Training (CT) is a digital method designed to enhance treatments like apimostinel. Since CT is non-invasive, there are no known safety issues.

Overall, both apimostinel and CT appear safe based on current data. However, researchers are still studying the long-term effects of apimostinel. Participants should feel reassured by the initial safety findings but are encouraged to ask questions if they have concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Apimostinel for depression because it works differently from most standard treatments, which often include SSRIs or SNRIs. Apimostinel targets the NMDA receptors in the brain, potentially offering faster relief from depressive symptoms. While typical antidepressants can take weeks to show effects, Apimostinel has the potential to act much quicker. Additionally, when combined with cognitive training, it may enhance cognitive functions, providing a dual benefit for individuals with depression.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that apimostinel quickly and effectively reduces depression symptoms in early studies. It works by affecting glutamate, a brain chemical that regulates mood. Patients in previous studies experienced significant improvements in their depression with this treatment. Apimostinel is also well-tolerated, with few side effects. In this trial, one group of participants will receive a combination of apimostinel and cognitive training, aiming to extend these positive effects. ^{1 2 3 4 6}

Who Is on the Research Team?

Rebecca B Price, PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for individuals with depression. Participants should be adults who can give informed consent and are in good general health. They must not have any serious risk of suicide or a history of substance abuse, and they cannot be on certain medications that would interfere with the study.

Inclusion Criteria

Clinical laboratory values < 1.5 times the upper limit of normal (ULN) or deemed not clinically significant per the investigator

MADRS score ≥ 25 at screening

Meets Diagnostic and Statistical Manual, Fifth Edition (DSM-V) criteria for major depressive disorder (MDD)

Exclusion Criteria

Changes made to treatment regimen within 28 days of drug infusion (Day 0)

History of allergy, sensitivity, or intolerance to specific substances

Presence of lifetime bipolar, psychotic, or autism spectrum; or current problematic, moderate-to-severe substance use disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous dose of Apimostinel or placebo, followed by Cognitive Training or Sham Training

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including MADRS and other scales

6 months

Multiple visits (in-person and virtual) from Day 1 to Month 6

What Are the Treatments Tested in This Trial?

Interventions

• Apimostinel
• Automated Neurocognitive Training

Trial Overview The trial is testing whether Apimostinel, given through an IV, can quickly relieve depression symptoms compared to a saline solution (a placebo). It also examines if Cognitive Training (CT) can make these benefits last longer than when no training or sham training is used.

How Is the Trial Designed?

Group I: Apimostinel + Cognitive Training Experimental Treatment 2 Interventions

Group II: Placebo + Cognitive Training Placebo Group 2 Interventions

Group III: Apimostinel + Sham Training Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

Rebecca Price

Lead Sponsor

Trials

8

Recruited

820+

Gate Neurosciences, Inc

Industry Sponsor

Trials

6

Recruited

850+

Syndeio Biosciences, Inc

Industry Sponsor

Published Research Related to This Trial

In a 1-year study involving 33 patients with early Alzheimer's disease, high doses of piracetam (8 g/day) did not show overall improvement in cognitive functions compared to placebo, but it may help slow cognitive decline.

The study found some significant differences in memory recall tasks, suggesting that while piracetam may not improve cognition, it could potentially slow the progression of memory deterioration in Alzheimer's patients, and it was well-tolerated by participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term and high-dose piracetam treatment of Alzheimer's disease. Croisile, B., Trillet, M., Fondarai, J., et al.[2019]

Anticholinesterase drugs, such as donepezil and rivastigmine, provide significant cognitive benefits for patients with mild-to-moderate Alzheimer's disease, although they can cause side effects in 5% to 15% of cases, including nausea and dizziness.

Memantine, an NMDA receptor antagonist, offers an alternative treatment for moderately severe to severe Alzheimer's disease by protecting neurons from harmful glutamate activity while supporting normal neurotransmitter function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of cognitive impairment in Alzheimer's disease. Burns, A.[2021]

A continuous transdermal delivery system for physostigmine was tested over 2 weeks in 12 Alzheimer's Disease patients, showing no major adverse effects and stable plasma concentrations of the drug.

Six out of 12 patients reported improvements in vigilance and concentration, with enhanced scores in neuropsychological tests, suggesting that this delivery method may be effective for some individuals with Alzheimer's Disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal physostigmine in the treatment of Alzheimer's disease. Levy, A., Brandeis, R., Treves, TA., et al.[2019]

In a 2-month randomized, double-blind, placebo-controlled trial involving 39 participants with mild Alzheimer's dementia, L-deprenyl showed no significant effects on cognitive or behavioral measures compared to placebo.

The study found that L-deprenyl did not improve clinical or neuropsychological outcomes, indicating it may not be an effective treatment for cognitive decline in mild dementia of the Alzheimer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-deprenyl in the treatment of mild dementia of the Alzheimer type: preliminary results. Burke, WJ., Ranno, AE., Roccaforte, WH., et al.[2019]

Donepezil hydrochloride is an effective treatment for mild-to-moderate Alzheimer's disease, showing benefits in cognition and global function, and it can delay nursing-home placement for patients.

The drug is well-tolerated with a long elimination half-life of 70 hours, and it does not cause liver toxicity or significant drug interactions, although caution is advised for patients with bradycardia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donepezil: a clinical review of current and emerging indications. Román, GC., Rogers, SJ.[2019]

In a double-blind, placebo-controlled trial involving 127 patients with dementia and mild depression, low doses of the antidepressant maprotiline (up to 75 mg/d) showed a significant antidepressant effect as measured by the Geriatric Depression Scale (GDS).

However, maprotiline did not improve cognitive performance, and video ratings of global impression indicated no beneficial effect of the treatment, highlighting that sedating antidepressants may not enhance cognitive functions despite alleviating depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Video rating analysis of effect of maprotiline in patients with dementia and depression. Fuchs, A., Hehnke, U., Erhart, C., et al.[2013]

In a study involving 17 Alzheimer's patients, both L-deprenyl and physostigmine were found to be safe and well tolerated, indicating no significant adverse effects during the treatment periods.

However, neither L-deprenyl nor physostigmine, alone or in combination, showed a significant improvement in cognitive function compared to placebo, suggesting limited efficacy in enhancing cognitive performance in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-deprenyl and physostigmine for the treatment of Alzheimer's disease. Marin, DB., Bierer, LM., Lawlor, BA., et al.[2019]

In a clinical trial involving 19 patients with major depressive disorder or bipolar disorder, scopolamine hydrobromide (4 microg/kg) demonstrated rapid and significant reductions in depression and anxiety symptoms compared to placebo, with improvements noted as early as the first evaluation after administration.

The study suggests that scopolamine may be a promising new antidepressant option, particularly for patients with poor prognoses, as it showed robust effects in alleviating depressive symptoms quickly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Furey, ML., Drevets, WC.[2022]

Citations

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Data on Allergan's Rapastinel and NRX-1074 (AGN ... During these first 2 to 6 weeks of traditional monoamine-based therapy, patients may continue to experience significant depressive symptoms, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6397075/

A new generation of antidepressants - PubMed Central - NIH Apimostinel/NRX-1074/AGN-241660, oral ... outcomes; descriptive efficacy measures showed large improvements in symptoms of depression and anxiety ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11486832/

Glutamatergic Modulators for Major Depression from Theory to ... In 2000, the first small study in people showed that ketamine, a medicine targeting glutamate, quickly improved depression symptoms.

4. synapse.patsnap.com synapse.patsnap.com/drug/90ba9a55b4324c5498a4842209ea0c2c

Apimostinel - Drug Targets, Indications, Patents Affecting about 30 % of major depressive disorder (MDD) patients, effective treatments for TRD are urgently needed. While depression research and ...

5. en.wikipedia.org en.wikipedia.org/wiki/Apimostinel

Apimostinel The drug has shown rapid and potent antidepressant effects in pre-clinical models of depression. In addition, similarly to rapastinel, it is well tolerated and ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1359644618303763

A new generation of antidepressants: an update on ... Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression ... Prognosis and improved outcomes in major depression: a review.