Glutamatergic Modulation for Post-COVID Depression

Overseen By Kate O'Malley, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: New York State Psychiatric Institute

Must not be taking: Psychotropics, Ritonavir, Benzodiazepines, others

Disqualifiers: Bipolar, Schizophrenia, Cardiac conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a medication that adjusts a brain chemical called glutamate to help people with long-term COVID-19 effects who are experiencing depression. Many studies have recently been conducted to assess the antidepressant efficacy of glutamate modification in mood disorders. The goal is to see if this treatment can improve their mood and mental clarity. The study involves giving the medication through infusions over several weeks.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those on psychotropic or other medications that could be disrupted by the study. It's best to discuss your current medications with the study team to see if they might affect your participation.

What evidence supports the effectiveness of the drug CI-581a, CI-581b for post-COVID depression?

Research shows that drugs like ketamine, which affect the glutamatergic system in the brain, can quickly reduce symptoms of depression, even in people who haven't responded to other treatments. This suggests that similar drugs, like CI-581a and CI-581b, might also help with depression, including post-COVID depression. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Research shows that ketamine, a glutamatergic modulator, has been used safely in clinical trials for depression, with fewer significant side effects when administered in lower doses. Other glutamatergic drugs have also been studied, showing varying safety profiles, but ketamine's rapid antidepressant effects have been consistently observed with manageable side effects. ^{1 2 4 6 7}

How does the drug CI-581a, CI-581b differ from other treatments for post-COVID depression?

The drug CI-581a, CI-581b is unique because it targets the glutamatergic system, which is different from traditional antidepressants that focus on monoamines like serotonin. This approach is inspired by the rapid-acting effects of ketamine, a known glutamatergic modulator, which has shown promise in treating depression by acting on NMDA receptors, potentially offering faster relief from depressive symptoms. ^{1 2 8 9 10}

Research Team

Saleena Subaiya, MD

Principal Investigator

New York State Psychiatric Institute

Elias Dakwar, MD

Principal Investigator

New York State Psychiatric Institute

Kate O'Malley, MA

Principal Investigator

New York State Psychiatric Institute

Eligibility Criteria

This trial is for English-speaking adults who've had COVID-19 and are now experiencing new or worsening depression, but are otherwise physically healthy. They must use effective birth control if sexually active, provide emergency contacts, have no severe reactions to the study drugs, and meet PASC criteria with depressive symptoms.

Inclusion Criteria

Capacity to consent and comply with study procedures, including sufficient proficiency in English

Sexually active participants must use an effective form of birth control (condom plus spermicide, diaphragm plus spermicide, or birth control pills) before and throughout their study participation

Willingness to provide one or more emergency contacts to the study team

Exclusion Criteria

You have been diagnosed with bipolar disorder, schizophrenia, or any psychotic illness according to the DSM-5 criteria.

You have been involved in a serious violent incident in the past two years that caused physical harm or led to police or legal involvement.

You have uncontrolled high blood pressure, anemia, liver disease, epilepsy, or untreated diabetes. If you have HIV, you may be asked about your current treatment. If you are taking a specific HIV medication called ritonavir (Norvir), you will not be able to participate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sub-anesthetic infusions of CI-581a and CI-581b in a randomized, double-blind, placebo-controlled pilot study

5 weeks

Multiple visits for infusion administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CI-581a
• CI-581b

Trial Overview The trial is testing two glutamate modulators (CI-581a and CI-581b) to see if they can help with depression in patients with long-COVID. It's a randomized, double-blind study which means participants won't know which treatment they're getting and neither will the researchers.

Participant Groups

Group I: CI-581b+CI-581a Experimental Treatment 2 Interventions

Administration of CI-581b at 0.025mg/kg during week 1. Administration of CI-581a at 0.8mg/kg during week 3.

Group II: CI-581a+CI-581b Experimental Treatment 2 Interventions

Administration of CI-581a at 0.8mg/kg during week 1. Administration of CI-581b at 0.025mg/kg during week 3.

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Findings from Research

Ketamine has shown a unique fast-acting neuroprotective and antidepressant effect by targeting the glutamatergic system, suggesting that glutamate plays a significant role in treating major depression.

Emerging treatments, including NMDA receptor antagonists and AMPA agonists, have demonstrated the ability to promote new synaptic connections and reverse stress-induced neuronal changes, indicating a promising direction for future antidepressant drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of calcium, glutamate and NMDA in major depression and therapeutic application. Deutschenbaur, L., Beck, J., Kiyhankhadiv, A., et al.[2015]

Excessive glutamate release is linked to stress and neurodegenerative diseases, and abnormalities in glutamatergic neurotransmission are significant in major psychiatric disorders like schizophrenia and depression.

Ketamine, an NMDA antagonist, shows rapid antidepressant effects for treatment-resistant depression, highlighting the potential of new antidepressants targeting the glutamate system, as supported by recent human studies using advanced imaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies. Li, CT., Yang, KC., Lin, WC.[2020]

References

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

Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Role of calcium, glutamate and NMDA in major depression and therapeutic application. [2015]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies. [2020]

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

Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Glutamatergic Treatments for Severe Mood Disorders. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Current Status of Ketamine and Related Therapies for Mood and Anxiety Disorders. [2020]

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

The involvement of glutamate in the pathophysiology of depression. [2005]

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

Glutamate-based depression GBD. [2013]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The NMDA receptor as a therapeutic target in major depressive disorder. [2019]