Post-Acute COVID-19, Inflammation, and Depression

Phase 2

Withdrawn

• Conditions: Post COVID -19 Depression
• Interventions: Biological: allogeneic marrow stromal cells (MSCs)

• Registration Number: NCT05346120
• Lead Sponsor: Sean Savitz

Brief Summary

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).

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 Timeline

• Study First Submitted: 2022-04-24
• Study First Submitted QC: 2022-04-24
• Study First Posted: 2022-04-26
• Study Start: 2022-05-25
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-05
• Last Update Posted: 2023-12-13
• Primary Completion: 2023-12-20
• Study Completion: 2024-05-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	allogeneic marrow stromal cells (MSCs)	Single IV infusion of 6 million cells/kg allogeneic marrow stromal cells (MSCs) lasting approximately 30 minutes
Placebo controlled	allogeneic marrow stromal cells (MSCs)	PlasmaLyte A supplemented with 5% HSA

Primary Outcome Measures

Name	Time	Method
Quick Inventory of Depressive Symptomatology (QIDS-SR)	from pre-infusion to Day 90	depression rating scale

Secondary Outcome Measures

Name	Time	Method
PROMIS	from pre-infusion to Day 90	Health related quality of life and scales measuring fatigue, pain, anger, anxiety