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

Trial Summary

What is the purpose of this trial?

Apimostinel shows initial promise as a novel rapid-acting antidepressant medication with minimal side effects or safety concerns. Cognitive Training (CT) is a digital intervention that has shown promise in extending the durability of another similar drug (ketamine). This randomized controlled trial will test the efficacy and safety of apimostinel (vs. placebo) for the acute treatment of depression, and will test the potential of CT to enhance and/or extend the durability of apimostinel's antidepressant effect.

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.

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

Research on the antimuscarinic drug scopolamine showed rapid reductions in depression severity, suggesting that targeting similar pathways might be effective for depression. While not directly related to Apimostinel, this indicates potential for drugs affecting neurotransmitter systems in treating depression. ^{1 2 3 4 5}

What makes Apimostinel unique for treating depression?

Apimostinel is unique because it combines a drug with cognitive training to treat depression, potentially offering a novel approach by enhancing brain function and mood simultaneously, unlike traditional antidepressants that primarily focus on chemical imbalances. ^{1 2 6 7 8}

Research Team

Rebecca B Price, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Apimostinel + Cognitive Training Experimental Treatment 2 Interventions

Group II: Apimostinel + Sham Training Placebo Group 2 Interventions

Group III: Placebo + Cognitive 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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

L-deprenyl and physostigmine for the treatment of Alzheimer's disease. [2019]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

L-deprenyl in the treatment of mild dementia of the Alzheimer type: preliminary results. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Donepezil: a clinical review of current and emerging indications. [2019]

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

Long-term and high-dose piracetam treatment of Alzheimer's disease. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Video rating analysis of effect of maprotiline in patients with dementia and depression. [2013]

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

Transdermal physostigmine in the treatment of Alzheimer's disease. [2019]