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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new treatments, CI-581a and CI-581b, to determine their effectiveness in helping people with long-COVID who have developed depression. The goal is to find out if these treatments can improve mood and reduce depressive symptoms. Participants will receive different combinations of these treatments to identify the most effective option. Individuals with long-COVID and new or worsening depression, who are otherwise healthy, might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that treatments like CI-581a and CI-581b are under study for their effects on depression following COVID-19. Earlier studies with similar treatments found that patients generally tolerated them well. Reported side effects were mild, such as dizziness or nausea, which are common with many medications. Although specific data on these exact treatments remains limited, their testing in a Phase 2 trial suggests early evidence of safety. This phase typically focuses on a treatment's safety and patient tolerance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for post-COVID depression because they target the glutamatergic system, which is different from most standard depression treatments that typically focus on serotonin. CI-581a and CI-581b are unique because they act on glutamate receptors, potentially offering faster results and benefits for patients who don't respond well to traditional antidepressants like SSRIs. This approach opens new possibilities for more rapid and effective relief from depressive symptoms following COVID-19.

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

This trial will evaluate the combination of CI-581a and CI-581b for depression related to long-COVID. Research has shown that these treatments can lead to small but important improvements in depressive symptoms a few weeks after use. This improvement can be crucial for people whose mental health has worsened after COVID-19. The treatments affect glutamate, a brain chemical that helps regulate mood. This approach appears promising for addressing the unique challenges of depression after COVID. ^{2 5 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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Trial | NCT05690503

New-onset depression, anxiety, and even suicidal behavior have also been reported. Symptoms of PASC can exhibit daily variation; additionally PASC frequently ...