Glutamatergic Modulation as a Treatment for Depressive Symptoms Among Patients With Post-acute Sequelae of COVID (PASC): A Pilot Trial

July 12, 2024 updated by: Elias Dakwar, New York State Psychiatric Institute
Post-acute sequelae of SARS-CoV2 (PASC), colloquially known as "long-COVID," is thought to affect between 10-30% of all COVID-19 survivors. Patients with PASC also report worsening behavioral health symptoms over time that include new-onset depression, anxiety, and even suicidal behavior. The purpose of this randomized, double-blind, controlled trial is to test the efficacy of a glutamate modulator among PASC patients suffering from new-onset or worsening of depressive symptoms.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

While PASC symptoms have been identified in nearly every organ system, the most common symptoms include fatigue, cognitive and attention deficits (known as 'brain fog'), shortness of breath, and post-exertional malaise. New-onset depression, anxiety, and even suicidal behavior have also been reported. Symptoms of PASC can exhibit daily variation; additionally PASC frequently demonstrates a relapsing and remitting course. This is mitigated by cognitive and emotional stress, physical exertion, diet, and alcohol consumption; therefore, measuring treatment response and the course of illness over time can be challenging. While there are many ongoing trials evaluating a variety of treatments for PASC, no clear treatment has emerged; additionally, there are no published data on psychotropic medications alleviating the inflammatory response and psychiatric symptoms in PASC.

Alterations in the transmission between neurons of a neurotransmitter called glutamate are an important target of pharmacotherapy for PASC. Glutamate modulators have demonstrated promise in improving depressive symptoms and suicidality and can improve cognitive functioning among patients with these symptoms. The study team has recently developed a novel design that integrates a clinical trial involving serial infusions. The current trial will evaluate the effect of a sub-anesthetic infusion on individuals with PASC and depressive symptoms who complete a randomized, double-blind, placebo-controlled pilot study conducted over 5 weeks using a cross-over and counterbalanced design.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Meeting the case-definition for PASC with depressive symptoms
  2. Otherwise physically healthy
  3. No adverse reactions to study medications
  4. Capacity to consent and comply with study procedures, including sufficient proficiency in English
  5. 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.
  6. Willingness to provide one or more emergency contacts to the study team

Exclusion Criteria:

  1. Meeting the DSM-5 criteria for lifetime history of bipolar disorder, schizophrenia, or any psychotic illness.
  2. Lifetime history of delirium, dementia, amnesia, or dissociative disorders
  3. Current suicide risk or a history of suicide attempt within the past year
  4. Pregnant or interested in becoming pregnant during the study period.
  5. Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia within 1 year of signing study consent form.
  6. Unstable physical disorders which might make participation hazardous such as hypertension (>160/90), anemia, active hepatitis or other liver disease (transaminase levels <3 X the upper limit of normal will be considered acceptable), epilepsy, or untreated diabetes. Participants reporting HIV+ status will be asked to provide information about their current treatment, including all medications. Participants who are on the antiretroviral ritonavir (Norvir) will be excluded due to the possibility that ketamine in combination with this medication may increase the risk of drug-induced hepatitis.
  7. Previous history of a substance use disorder with the study medications, and/or a history of an adverse reaction/experience with prior exposure to the study medications.
  8. Recent history of significant violence (past 2 years) leading to an individual incurring physical harm, police involvement, or resulting in legal action.
  9. On psychotropic or other medications whose effect could be disrupted by participation in the study.
  10. Other personal circumstances and behavior judged to be incompatible with establishment of rapport or safe exposure to the study medications.
  11. Physiologic dependence on a substance including benzodiazepines, alcohol, or opioids.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CI-581a+CI-581b
Administration of CI-581a at 0.8mg/kg during week 1. Administration of CI-581b at 0.025mg/kg during week 3.
Drug: CI-581a
Medication infusion intravenously over 90 minutes.
Drug: CI-581b
Medication infusion intravenously over 90 minutes.
Experimental: CI-581b+CI-581a
Administration of CI-581b at 0.025mg/kg during week 1. Administration of CI-581a at 0.8mg/kg during week 3.
Drug: CI-581a
Medication infusion intravenously over 90 minutes.
Drug: CI-581b
Medication infusion intravenously over 90 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Reduction in depressive symptoms
Time Frame: from baseline to week 5.
from baseline to week 5.

Secondary Outcome Measures

Outcome Measure
Time Frame
Improvement in neurocognitive symptoms of PASC
Time Frame: from baseline to week 5.
from baseline to week 5.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Investigators

  • Principal Investigator: Saleena Subaiya, MD, New York State Psychiatric Institute
  • Principal Investigator: Elias Dakwar, MD, New York State Psychiatric Institute
  • Study Director: Kate O'Malley, MA, New York State Psychiatric Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2023

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

December 30, 2022

First Submitted That Met QC Criteria

January 17, 2023

First Posted (Actual)

January 19, 2023

Study Record Updates

Last Update Posted (Actual)

July 16, 2024

Last Update Submitted That Met QC Criteria

July 12, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8336 (CTEP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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