Post-Acute COVID-19, Inflammation, and Depression (COVID Long)

Single site, double blind, placebo-controlled, longitudinal study of depression in Subjects with COVID- 19 long haulers syndrome using a 1:1 ratio randomization for a single IV infusion of 6 million cells/kg allogeneic marrow stromal cells (MSCs).

Study Overview

• Status: Withdrawn
• Conditions: Post COVID -19 Depression
• Intervention / Treatment: Biological: allogeneic marrow stromal cells (MSCs)

Detailed Description

A prospective study evaluating depression in COVID- 19 long haulers syndrome treated with allogeneic marrow stromal cells. Accruing evidence suggests cognitive and affective dysfunction, depression, and fatigue occur after COVID-19 infection. These impairments, likely arise from multiple factors that may include cell/organ damage due to direct viral infection or inflammatory process. The current proposal hypothesizes that the inflammatory response is a critical mechanism underlying these neuropsychiatric conditions.

After recovery from COVID-19, the hyperimmune activity secondary to tissue damages and endothelial activation may leave post-acute COVID-19 patients vulnerable to the neural consequences of proinflammatory cytokines Heightened inflammation can alert the central nervous system to induce sickness behaviors and elevated risk of depression.

We hypothesize that allogeneic marrow stromal cells (MSCs) will attenuate post-covid inflammation and reduce the resulting neuropsychiatric symptoms.

Aim 1: Evaluate the feasibility and acceptability of recruiting, providing MSC/sham infusions, and following participants to collect biomarker and clinical outcomes.

• MSC's infusions, baseline and follow-up measurements will be feasible and acceptable to participants.

Aim 2: Estimate the probability of demonstrating improvement in depression (i.e. > 30% reduction on the MADRS) among adult patients experiencing post-COVID depression randomized to MSC Infusion versus Sham Infusion. To determine (obtain, evaluate, verify, etc.) …

• MSC Infusion will out-perform Sham Infusion on the proportion of MADRS responders.

Aim 3: Relative to usual care, estimate the differential improvement of MSC-treated participants on cognitive measures and PROMIS (Health-Related Quality of Life; HRQOL) scales (e.g. Fatigue, Pain, Anger, Anxiety, etc.).

• MSC Infusion will out-perform Sham Infusion +on improvements in cognitive function and HRQOL measures.

Aim 4: Estimate the change attributable to MSC treatment on a panel of inflammatory biomarkers relative to usual care.

• Relative to Sham Infusion, MSC Infusion will down-regulate pro-inflammatory processes while upregulating anti-inflammatory processes, and this modulation will be related to improvement in depression, cognitive and PROMIS measures. Relative to Sham Infusion, MSC Infusion will down-regulate pro-inflammatory processes while upregulating anti-inflammatory processes, and this modulation will be related to improvement in depression, cognitive, and PROMIS measures.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. The subject, or legally authorized representative, must be able to understand and voluntarily sign an informed consent document 2. Diagnosed with COVID-19 within the last 90 days 3. Age 18 to 80 years 4. QIDS-SR> 11

Exclusion Criteria:

• 1. A pre-COVID-19 history of cognitive dysfunction, or chronic fatigue 2. Exclude Recurrent episodes of depression (allowed: a prior episode but completed medication at least 3 months before enrollment) 3. Any medical or psychiatric condition which could confound study assessments 4. Stroke within the last 3 months 5. Developmental delay 6. Any other condition that the investigator feels would pose a significant hazard to the patient if enrolled 7. Current participation in any interventional research study 8. Unable to return for follow-up visits for clinical evaluation, laboratory studies, or imaging evaluation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Single IV infusion of 6 million cells/kg allogeneic marrow stromal cells (MSCs) lasting approximately 30 minutes	Biological: allogeneic marrow stromal cells (MSCs); stem cell infusion
Placebo Comparator: Placebo controlled; PlasmaLyte A supplemented with 5% HSA	Biological: allogeneic marrow stromal cells (MSCs); stem cell infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depressive Symptomatology (QIDS-SR)	depression rating scale	from pre-infusion to Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS	Health related quality of life and scales measuring fatigue, pain, anger, anxiety	from pre-infusion to Day 90

Collaborators and Investigators

• Sponsor: Sean Savitz
• Investigators: Study Director: Susan E Alderman, PhD, UTHealth Science Center Houston

Study record dates

Study Major Dates

• Study Start (Estimated): May 25, 2022
• Primary Completion (Estimated): December 20, 2023
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: April 24, 2022
• First Submitted That Met QC Criteria: April 24, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Inflammation
• Other Study ID Numbers: COVID long

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No