Cognitive Dysfunction Interventions for Long COVID

No longer recruiting at 24 trial locations

Overseen By Barrie Harper, BSMT (ASCP) PMP

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Stimulants, Amantadine, Memantine, Dissociatives

Disqualifiers: Major psychiatric, Neurologic, Substance use, others

Compensation: Varies

Number of Visits: 5

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to improve cognitive issues, such as focus and decision-making problems, in individuals who have experienced Long COVID. It will test various treatments, including mental exercises (like BrainHQ), group activities, and brain stimulation (such as transcranial direct current stimulation, or tDCS). The goal is to determine if these methods can aid those struggling with cognitive problems after COVID-19. Individuals who have had COVID-19 and continue to experience cognitive difficulties for at least 12 weeks may be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to investigate innovative treatments for cognitive recovery after Long COVID.

Do I have to stop taking my current medications to join the trial?

The trial requires that you stop using certain medications, like stimulants and some other specific drugs. If you're currently using these, you may need to stop before joining the trial.

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

Research shows that BrainHQ is generally safe and well-tolerated. This brain training program has been used safely in many studies, with serious side effects being rare.

When combined with PASC CoRE, evidence suggests that these brain rehabilitation methods can be safe and effective. They are typically adapted from programs proven safe in other studies.

For BrainHQ combined with tDCS-active, research indicates that transcranial direct current stimulation (tDCS) is usually safe. Participants might feel mild tingling or warmth on the scalp, but serious side effects are uncommon.

While this trial doesn't yet have specific safety data, similar studies have shown these treatments to be well-tolerated. Any concerns should be discussed with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for cognitive dysfunction in Long COVID because they offer innovative approaches beyond current standard therapies, like cognitive rehabilitation and pharmacological treatments. BrainHQ, for instance, is a digital cognitive training program that's structured to be highly interactive and adaptive to individual needs. The combination of BrainHQ with PASC CoRE introduces a comprehensive format with both group and individual sessions, allowing for a more tailored approach. Meanwhile, the BrainHQ paired with tDCS-active treatment uses non-invasive brain stimulation to potentially enhance cognitive training effects, which is a novel method compared to traditional cognitive interventions. These features could provide new avenues for more effective management of cognitive symptoms in Long COVID patients.

What evidence suggests that this trial's treatments could be effective for cognitive dysfunction in Long COVID?

Research has shown that BrainHQ, an online brain training program, can improve thinking skills in people with memory and attention problems, including those with Long COVID. Studies have found it helps with issues like brain fog and makes daily activities easier. In this trial, some participants will receive BrainHQ alone, while others will receive BrainHQ combined with additional interventions.

When used with PASC CoRE, which includes group and individual sessions, studies suggest BrainHQ may further boost recovery by focusing on specific thinking problems related to Long COVID. This combination is one of the treatment arms in this trial.

Additionally, combining BrainHQ with tDCS-active, a method that uses a small electrical current on the brain during training, is another treatment arm being studied. Research suggests this can help Long COVID patients by improving the brain's ability to learn and adapt. ^{5 6 7 8 9}

Who Is on the Research Team?

Kanecia Zimmerman, MD PhD

Principal Investigator

Duke University

Daniel Laskowitz, MD MHS

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

Adults over 18 who've had cognitive issues for at least 12 weeks after COVID-19, scoring below 40 on a cognitive test. They must have had symptoms like fever and cough or been in contact with a confirmed case. Participants need to speak English or Spanish and can't be using certain drugs for neurological conditions, substance abuse disorders, or other clinical trials.

Inclusion Criteria

Willing and able to provide informed consent, complete the intervention, complete the intervention assessments, and return for all of the necessary follow-up visits

I have had COVID-19 before.

I have had thinking or memory problems for over 12 weeks after a COVID-19 infection.

Exclusion Criteria

I have been diagnosed with chronic fatigue syndrome not due to COVID-19.

I am currently using a stimulant for post-COVID symptoms.

You have a serious mental or neurological condition that is unstable or getting worse, and it could make it hard to see if the treatment is working.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo various cognitive interventions, including BrainHQ sessions and potential additional treatments like tDCS or PASC CoRE

10 weeks

5 sessions/week

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BrainHQ
• BrainHQ/Active Comparator Activity
• PASC CoRE
• tDCS-active
• tDCS-sham

Trial Overview The trial is testing different treatments for long-term cognitive problems after COVID-19. It includes active tDCS (a brain stimulation technique), sham tDCS (placebo), BrainHQ exercises, and PASC CoRE activities. The study randomly assigns participants to these interventions to see which helps improve attention and executive function.

How Is the Trial Designed?

Group I: BrainHQ + PASC CoRE Experimental Treatment 2 Interventions

BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 30 min/session

Group II: BrainHQ Experimental Treatment 1 Intervention

5 sessions/week at 30 min/session

Group III: Brain HQ + tDCS-active Experimental Treatment 2 Interventions

2.0 mA stimulation delivered for 30 min during each BrainHQ session

Group IV: BrainHQ Active Comparator Active Control 1 Intervention

5 sessions/week at 30 min/session

Group V: Brain HQ + tDCS-sham Placebo Group 2 Interventions

Inactive stimulation delivered for 30 min during each BrainHQ session

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11418572/

Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection ... The most common symptoms include fatigue, cognitive impairment (brain fog), and shortness of breath. ... SARS-CoV-2 can alter mitochondrial function, which ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0003999324007779

Long COVID (Post Acute Sequelae of SARS-CoV-2 ... Clinical improvements of various symptomatology including olfactory, cognitive and memory dysfunction, fatigue, visual field, and quality of life were noted ...

3. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08156-z

RECOVER-NEURO: study protocol for a multi-center ... - Trials This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions ...

4. brainhq.com brainhq.com/news/press-releases/study-shows-large-improvements-in-long-covid-symptoms-and-return-to-work/

Study Shows Large Improvements in Long COVID ... ... cognitive impairment and with dysfunction in the performance of instrumental activities of daily living. ... brain health and function. He ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05389592

Treatment of COVID-19 Post-acute Cognitive Impairment ... In fact, a point of convergence between AD and the cognitive sequelae of COVID-19 would be precisely autonomic dysfunction - chronic, progressive and of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8260991/

Long COVID or Post-acute Sequelae of COVID-19 (PASC) This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences.

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2805540

Development of a Definition of Postacute Sequelae ... This study aims to develop a definition of postacute sequelae of SARS-CoV-2 infection (PASC) based on self-reported symptoms and describe ...

8. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00177-3/fulltext

Long-term post-acute sequelae of COVID-19 infection This study aims to generate coherent evidence on the risk of long-term clinical sequelae of patients recovering from COVID-19 infection using ...

9. nature.com nature.com/articles/s41591-023-02521-2

Postacute sequelae of COVID-19 at 2 years SARS-CoV-2 infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection.