Cognitive Rehabilitation for Long COVID (STAR-C3)

January 21, 2025 updated by: McMaster University

Symptom-Targeted Rehabilitation for Cognitive Complaints in Long COVID (STAR-C3)

The investigators are comparing two different methods for helping adults with Long Coronavirus (COVID) also known as Post-Coronavirus Syndrome or Post-Coronavirus Condition manage everyday cognitive challenges. Cognitive rehabilitation is a type of therapy that helps people who have challenges with everyday thinking because of a brain injury. One of the investigators on this project along with colleagues in the United States (US) have developed a streamlined version of cognitive rehabilitation therapy for mild traumatic brain injury (mTBI) that can be completed in person or virtually and takes place over a 3-week period. The therapy was originally designed for adults with mTBI. The investigators want to know if it can also be used to treat people with cognitive complaints from Long COVID. The investigators will provide education materials only to one group and individual cognitive rehabilitation delivered by a trained Speech Language Pathologist (SLP) or Occupational Therapist (OT) to the other group. The investigators want to find out whether the individual therapy is as feasible and accessible than the usual educational material. What the investigators learn in this study may help treat day-to-day thinking challenges in Long COVID.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cognitive complaints are one of the most common, pervasive, and debilitating outcomes for adults with Long COVID. In a study of 3762 adults from 56 countries who were 7 months post-diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS Coronavirus 2, referred to here as COVID) 85% reported cognitive problems, including brain fog, word-finding problems, difficulty communicating their thoughts, and a reduced ability to solve serious problems. In the Great British Intelligence Test, an online study of 81,337 individuals the subgroup of 12,689 who reported having had COVID had significantly lower cognitive test scores than those who had not, providing objective support for the symptoms that adults with Long COVID are reporting. These persistent cognitive symptoms, which the investigators refer to as Post-COVID Cognitive Symptoms (PCCS), do not appear to spontaneously resolve, with many patients in Canada and worldwide reporting cognitive impairments more than 1 year after infection. PCCS can have severe effects on usual functioning, particularly given that most survivors are working age. Two large studies estimated that at 7-9 months post-infection, between 40-75% of adults either could not work at all or were working fewer hours than they did pre-COVID. Although emerging data indicate that PCCS may be less common after infection with the Omicron variant, there continues to be concern about future "super-variants" that may have more virulent effects. Even if infection rates stabilize, i.e., COVID becomes endemic, the disease does not become harmless.

Usual care for those with PCCS is, at best, providing information about how to manage symptoms (e.g., this handout from the Public Health Authority of British Columbia). The literature on treatment of cognitive problems in other patient groups, however, shows that providing general information alone does not "fix" cognitive impairments. To improve cognitive function in everyday life, intervention must be individualized and provide opportunities for high-dose practice of target behaviours. The investigators do not, however, have interventions like this with demonstrated effectiveness for PCCS. The literature related to cognitive rehabilitation after COVID includes three types of papers: 1) studies of COVID effects on people who had cognitive diagnoses pre-COVID (e.g., how lack of services has affected patients with Alzheimer's Disease) 2) a small number of case reports of rehabilitation for COVID patients, in which cognitive rehabilitation is mentioned in general terms (e.g., patient received "skill training for basic activities of living" and "evaluation of adaptive devices", and 3) urgent calls for cognitive rehabilitation of adults with PCCS (e.g., 13-15). To the investigators knowledge, there are no published controlled studies of cognitive rehabilitation methods for adults with PCCS. One of the investigators recently completed a pilot pre-post study with 34 adults with Long COVID to examine if physical therapy for physical symptoms and occupational therapy for cognitive symptoms was safe and feasible (protocol completed, under analysis). The cognitive intervention was 6 hours of combined individual and group cognitive rehabilitation over 12 weeks, including education about managing cognitive challenges. The pilot data showed a reduction in intensity and frequency of cognitive symptoms, but no effect on everyday functioning. The study investigators concluded that to improve everyday function, therapy must be targeted at individual complaints, and it is this type of intervention that the investigators propose for a randomized control trial (RCT).

A recent paper in Science 16 called for cognitive rehabilitation to be part of the health system response to Long COVID, but rehabilitation was not included in the category of research needs - i.e., the paper implied that investigators already know how to treat patients with PCCS, and that investigators just need to increase access to therapy. However, it is unclear if standard cognitive rehabilitation methods used for other patient groups are effective for people with PCCS. One source of guidance for PCCS rehabilitation methods is the literature on cognitive rehabilitation for adults with traumatic brain injury (TBI), especially patients with mild TBI (aka concussion). Adults with mild TBI (mTBI) have symptoms that are commonly reported by adults with PCCS, such as word-finding problems, slow thinking, "brain fog", trouble following instructions, forgetting medications, difficulty in conversations, complaints about mental fatigue, and difficulty making decisions. There also is anecdotal evidence from clinicians who have overseen treatment of more than 3400 adults with Long COVID - that PCCS characteristics are very similar to patients with mild TBI. COVID and TBI share pathophysiological features such as inflammation, hypoxia, microvascular lesions and disruption of the blood-brain barrier, cortical thinning, and diffuse white-matter damage, particularly in anterior cortical regions. Best practices in cognitive rehabilitation also should be similar in both groups: treatments must be tailored to the patients needs, focused on solving everyday thinking challenges rather than 'fixing' deficits, and given in a relatively high dose.

In summary, PCCS is prevalent, debilitating, and persistent, and there is a lack of evidence-based methods to treat adults with these problems. TBI and COVID share pathophysiological features, survivors report similar cognitive symptoms, and best practices apply to both populations, thus the investigators predict that cognitive rehabilitation methods developed for adults with mTBI will also be effective for adults with PCCS.

Study design will follow recommendations in the CONSORT extension for randomized pilot and feasibility trials, so that data from the Vanguard study can be used in the main trial analysis. Results of the main study will significantly advance the investigators understanding of health consequences of COVID-19, delivery of health care, and health outcomes for adults with Long COVID. It is interdisciplinary research by a Canadian-led research team representing speech-language pathology, occupational therapy, physiotherapy, healthcare administration, and stakeholders with lived experience; and includes US collaborators representing the largest national company providing a cognitive rehabilitation program developed specifically for adults with Long COVID. The investigators collaboration with US partners is a step toward globalization of the rehabilitation methods.

The investigators propose to complete a Vanguard two-arm RCT of STAR-C3 with 100 adults randomized to either Therapy (n=50) or Education (n=50) groups. The study aims to demonstrate the acceptability, appropriateness, and feasibility of STAR-C3 as judged by clinicians and participants with PCCS. Therapy will be delivered by an Occupational Therapist (OT) or Speech-Language Pathologist (SLP).

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

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

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada
        • McMaster University

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 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Is a community-dwelling adults
  • Is age 18 years or older
  • Self-identifies as a fluent English speaker
  • Have a history of COVID symptoms as listed on the Government of Canada COVID information website, a positive antigen or polymerase chain reaction (PCR) test, or both
  • Have cognitive symptoms that have persisted a minimum of 12 weeks after contracting COVID
  • Have cognitive symptoms attributable to COVID and not to other intervening diagnoses associated with cognitive dysfunction (e.g., psychosis, concussion), or medications with negative effects on cognitive function
  • Have no previous history of a diagnosis of a neurological disorder affecting thinking (e.g., dementia)
  • Are able to participate in 3 one-hour sessions per week for 4-6 weeks
  • Are not in active behavioural treatment for a substance-use or mental-health disorder, or in cognitive rehabilitation provided by a registered health professional (e.g., speech-language pathologist or occupational therapist)
  • Can access an electronic device with internet access and capability for Zoom videoconferencing

Exclusion Criteria:

  • A score of less than 20 on the Montreal Cognitive Assessment (MoCA), which indicates a risk for dementia.
  • Cannot identify at least 3 problems on the Common Cognitive Complaints after Concussion Questionnaire (C4), as there would be insufficient areas for intervention.

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: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Therapy Group
The Therapy Group will receive 6-10 individual sessions of 30-60 minutes each, delivered by a trained Occupational Therapist or Speech-Language Pathologist. The therapy will be delivered over a 4-week timeframe, with the total number of sessions per participant depending on the number of sessions needed to achieve their treatment targets. Each participant in the Therapy Group will identify three cognitive targets for treatment. Progress in reaching those targets will be documented using Goal Attainment Scaling (GAS)
Behavioral: Cognitive Rehabilitation
A strategy-focused intervention aimed at improving everyday cognitive function, structured to maximize treatment dose over a short time period. The shorter time period of the treatment therapy is relative to the one and only current randomized controlled trial of cognitive rehabilitation for military mTBI, the Study of Cognitive Rehabilitation Effectiveness (SCORE).
Active Comparator: Educational Group
The Education group will receive information about self-management of cognitive symptoms at the time of randomization, a common alternative for adults with Long COVID cognitive symptoms who do not receive Individual Therapy.
Other: Education
The Education group will receive information about self-management of cognitive symptoms at the time of randomization, a common alternative for adults with Long COVID cognitive symptoms who do not receive Individual Therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recruitment Rate
Time Frame: 9 months
The primary outcome is the rate of recruitment, average 5 per month. The primary outcome is the rate of recruitment and retention rate reported as the total number of participants recruited and retained.
9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acceptability of the Intervention
Time Frame: Measures administered during intake (baseline), immediately after one of sessions 6-10 depending on targets achieved, and 1 month post-treatment.
The acceptability will be assessed by clinicians and participants. At least three quarters of participants and clinicians will provide a rating of 4 on the Acceptability of Intervention Measure (AIM).
Measures administered during intake (baseline), immediately after one of sessions 6-10 depending on targets achieved, and 1 month post-treatment.
Acceptability of the Appropriateness
Time Frame: Measures administered during intake (baseline), immediately after one of sessions 6-10 depending on targets achieved, and 1 month post-treatment.
The acceptability will be assessed by clinicians and participants. At least three quarters of participants and clinicians will provide a rating of 4 on the Intervention Appropriateness Measure (IAM).
Measures administered during intake (baseline), immediately after one of sessions 6-10 depending on targets achieved, and 1 month post-treatment.
Acceptability of the Feasibility
Time Frame: Measures administered during intake (baseline), immediately after one of sessions 6-10 depending on targets achieved, and 1 month post-treatment
The acceptability will be assessed by clinicians and participants. At least three quarters of participants and clinicians will provide a rating of 4 on the Feasibility of Intervention Measure (FIM).
Measures administered during intake (baseline), immediately after one of sessions 6-10 depending on targets achieved, and 1 month post-treatment

Collaborators and Investigators

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

Sponsor

McMaster University

Collaborators

Canadian Institutes of Health Research (CIHR)

Investigators

  • Principal Investigator: Jackie Bosch, PhD, McMaster University School of Rehabilitation Science
  • Principal Investigator: Lyn Turkstra, PhD, McMaster University School of Rehabilitation Science

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

May 1, 2023

Primary Completion (Actual)

January 21, 2025

Study Completion (Actual)

January 21, 2025

Study Registration Dates

First Submitted

January 4, 2023

First Submitted That Met QC Criteria

January 4, 2023

First Posted (Actual)

January 9, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 21, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15621

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

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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