Cognitive ImpairmentPhase 4NCT05597722
Addressing Cognitive Fog in Long-COVID-19 Patients
A Phase 4 study testing Digital cognitive behavioral intervention-RxWell and Amphetamine-Dextroamphetamine in people with Cognitive Impairment and Long COVID, run by Eva Szigethy at 1 site in United States.
Trial summary
This study will assess two options to help patients better manage the cognitive fog and emotional distress that may be associated with having Long-COVID. Long-COVID is post-COVID conditions or symptoms lasting more than four weeks after infection. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Cognitive Impairment, Long COVID
- What is being tested?
- Digital cognitive behavioral intervention-RxWell and Amphetamine-Dextroamphetamine
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2023to 18 May 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of SARS-CoV-2 infection as defined as a positive PCR or home antigen test
- Patients with Long-COVID as defined as COVID symptoms that persist for three months or longer.
- Between the ages of 21 and 65
- Moderate cognitive impairment (MOCA score to meet criteria is < or =18) present for at least 3 months
- Response of "No" to the screening question, "Are you pregnant or do you plan to become pregnant in the next 3 months?"
- Access to a smartphone
Who cannot join
- History of dementia, psychosis, mania, addiction or current conditions requiring immediate hospitalization
- Previous adverse or allergic reaction to Adderall or other amphetamines
- Pre-existing cardiac or kidney condition, severe hypertension, glaucoma, advanced arteriosclerosis, hyperthyroidism, and taking an MAOI within the past 14 days
- Current or past substance misuse
- Previous use of RxWell (completed 3 or more techniques)
- Current use of amphetamine-dextroamphetamine
Show all 9Show fewer
- History of uncontrolled blood pressure
- Subjects taking Methylphenidate; Lisdexamfetamine; non-Adderall amphetamine products; Atomoxetine; Viloxazine; Modafinil; Armodafinil; Nortriptyline and other tricyclic drugs; Bupropion; Tramadol; and Monoamine Oxidase Inhibitor (MAOI) drugs (including Linezolid).
- Inability to pay for study medication.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Randomized Study to Evaluate Strategies to Address Cognitive Fog in Long-COVID-19 Patients
This study will assess two options to help patients better manage the cognitive fog and emotional distress that may be associated with having Long-COVID. Long-COVID is post-COVID conditions or symptoms lasting more than four weeks after infection. Clinicians from the UPMC Long-COVID Clinic leading this study are evaluating the utility of computer-based evaluation of COVID-related cognitive fog and the helpfulness of two intervention strategies to treat moderate cognitive impairment using a randomized trial. The two intervention strategies include 1) a standardized dosing of amphetamine/dextroamphetamine medication that has been used to improve cognitive fog; and 2) a digital behavioral tool with an embedded health coach that is used on a mobile phone.
Read the detailed description
Eligible participants will be randomized to one of two arms. One intervention targets cognitive fog associated with depression (RxWell mobile app), the other the cognitive fog directly (Amphetamine-dextroamphetamine medication). Two weeks after randomization, participants are contacted by study staff to complete the GAD7. Participants who are randomized to RxWell will be offered assistance if they were not able to download the app on their own. Participants who are randomized to receive the stimulant will also complete a stimulant drug side effect rating scale to determine if the participant has any effects from the medication.
All participants will complete computerized neurocognitive assessments (ImPACT, and BrainCheck) and other study measures (MOCA (Screen, 1.5 and 3 months), Patient Health Questionnaire, Generalized Anxiety Disorder Measure, Satisfaction with Life Scale, PCL-5 Post Traumatic Stress Disorder checklist, ADHD Symptom Screener, and Sheehan Disability Scale) at baseline, 1.5 (interim) and 3 months after randomization. The study measures, other than the neuro-cognitive assessments, will be completed via REDCap.
- Conditions
- Cognitive Impairment, Long COVID
- Being tested
- Digital cognitive behavioral intervention-RxWell, Amphetamine-Dextroamphetamine
- Keywords
- Cognitive fog, Long-COVID
- Medical subject headings
- Cognitive Dysfunction, Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Digital cognitive behavioral intervention-RxWellBehavioural
RxWell is a coach enhanced digital behavioral health intervention that teaches techniques to help manage emotional distress, which may improve cognitive fog and/or depression. Participants will have access to this app for three months.
Amphetamine-DextroamphetamineDrug
Also called Adderall
Participants randomized to this arm will be prescribed 10mg of amphetamine-dextroamphetamine to take as needed to help with cognitive fog. Participants in this arm will be contacted at 2 and 6 weeks to assess for any side effects from taking the medication.
| Study group | Role | What they receive |
|---|---|---|
| Digital cognitive behavioral intervention- RxWell | Active comparator | The mobile app provides users with brief skill building techniques such as relaxation, behavioral activation and exposure, distress tolerance, cognitive reframing, and mindfulness meditation, for anxiety and depression. The content of RxWell was developed based on standard CBT techniques for treating anxiety disorders and depression. The user will have the option to select either the depression or anxiety program, and the coach will have the ability to personalize the program so that the individual can utilize the proper CBT techniques that fits with their presentation.
The health coach communicates with RxWell users via asynchronous, secure within app messaging. They reinforce CBT principles, guide users through goal setting, and help users work through challenges and recognize successes. The coaches will also receive individualized cognitive rehabilitation tips from the speech therapist after their appointment with the participant. Receives: Behavioral: Digital cognitive behavioral intervention-RxWell |
| Stimulant Medication | Active comparator | The other intervention is a stimulant medication known to reduce cognitive impairment in other chronic medical conditions, such as Inflammatory Bowel Disease. The Long-COVID psychiatrist will order the medication and the participant will be scheduled for a 6-week research tele visit with the psychiatrist to monitor for any medication side effects. Amphetamine-dextroamphetamine drug dose will be 10mg daily for 12 weeks, and no dose changes will be made. Amphetamine-dextroamphetamine is a Schedule II controlled substance that has a risk for abuse, tolerance, and psychological dependence, which can be associated with severe social disability. Receives: Drug: Amphetamine-Dextroamphetamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cognitive Impairment - MOCA
The MOCA is a validated screening tool that provides a total score to assess for mild cognitive impairment.
Measured: Compare baseline to 12 weeks
Change in Cognitive Impairment - BrainCheck
BrainCheck is an FDA approved validated, automated, remote neurocognitive assessments in multiple domains.
Measured: Compare baseline to 12 weeks
Change in Cognitive Impairment - ImPACT
ImPACT is an FDA approved computerized neurocognitive concussion assessment tool that provides composite sores to evaluate cognitive abilities.
Measured: Compare baseline to 12 weeks
Secondary outcomes (3)
Change in Depression - PHQ8
Patient Health Questionnaire (PHQ8) will be utilized to measure change in depression severity from baseline up to 12 weeks after baseline.
The PHQ-8 is an 8 item questionnaire. Scores can range from 0-24. A score of 0-4 indicates no depressive symptoms; 5-9 indicates mild depressive symptoms; 10-19 indicates moderate depressive symptoms; 20-24 indicates severe depressive symptoms.
Measured: Compare baseline up to 12 weeks
Change in Quality of Life - SWLS
Satisfaction with Life Scale (SWLS) will be utilized to measure change in quality of life from baseline up to 12 weeks after baseline.
SWLS is a five item measure with a maximum score of 35. Higher score correlate with higher satisfaction of life. Scores 31-35 extremely satisfied. Scores less than 9 indicate extremely dissatisfied.
Measured: Compare baseline up to 12 weeks
Change in Disability
Sheehan Disability Scale assess functional impairment in three inter-related domains; work/school, social and family life. The three items are summed into a single measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).
Measured: Compare baseline up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2022
- Study start4 Apr 2023
- Primary completion18 May 2023
- Study completion18 May 2023
Why it stopped: Due to the evolving nature of COVID-related cognitive fog, it was determined that the study would be terminated at this time. The team agreed that it isn't feasible to collect enough data to evaluate the efficacy of the treatments.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized 1:1 block design trial evaluating the effect of a digital cognitive behavioral app versus a drug therapy (amphetamine-dextroamphetamine \[Adderall\]) on cognitive impairment and other secondary outcomes in subjects with post-COVID symptoms (Long-COVID). The participants will be stratified by depression severity.
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eva Szigethy
- Sponsor type
- University, hospital or other
- Collaborators
- The Beckwith Institute
- Responsible party
- Sponsor-investigator, Eva Szigethy, University of Pittsburgh
- Investigators
- Eva Szigethy, MD, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05597722
- Sponsor's protocol ID
- STUDY22050191
- Status last verified
- May 2023
- First submitted
- 27 Oct 2022
- Last updated
- 22 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared. Data is shared at the aggregate level.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Study to Evaluate Strategies to Address Cognitive Fog in Long-COVID-19 Patients
- ClinicalTrials.gov ID
- NCT05597722
- Acronym / sponsor ID
- STUDY22050191
- Conditions
- Cognitive Impairment, Long COVID
- Keywords
- Cognitive fog, Long-COVID
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the evolving nature of COVID-related cognitive fog, it was determined that the study would be terminated at this time. The team agreed that it isn't feasible to collect enough data to evaluate the efficacy of the treatments.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Eva SzigethyUniversity, hospital or other
- Collaborators
- The Beckwith Institute
- Study start
- 4 Apr 2023 (actual)
- Primary completion
- 18 May 2023 (actual)
- Study completion
- 18 May 2023 (actual)
- First posted
- 28 Oct 2022 (actual)
- Results
- Posted 22 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess two options to help patients better manage the cognitive fog and emotional distress that may be associated with having Long-COVID. Long-COVID is post-COVID conditions or symptoms lasting more than four weeks after infection. Clinicians from the UPMC Long-COVID Clinic leading this study are evaluating the utility of computer-based evaluation of COVID-related cognitive fog and the helpfulness of two intervention strategies to treat moderate cognitive impairment using a randomized trial. The two intervention strategies include 1) a standardized dosing of amphetamine/dextroamphetamine medication that has been used to improve cognitive fog; and 2) a digital behavioral tool with an embedded health coach that is used on a mobile phone.
Detailed description
Eligible participants will be randomized to one of two arms. One intervention targets cognitive fog associated with depression (RxWell mobile app), the other the cognitive fog directly (Amphetamine-dextroamphetamine medication). Two weeks after randomization, participants are contacted by study staff to complete the GAD7. Participants who are randomized to RxWell will be offered assistance if they were not able to download the app on their own. Participants who are randomized to receive the stimulant will also complete a stimulant drug side effect rating scale to determine if the participant has any effects from the medication.
All participants will complete computerized neurocognitive assessments (ImPACT, and BrainCheck) and other study measures (MOCA (Screen, 1.5 and 3 months), Patient Health Questionnaire, Generalized Anxiety Disorder Measure, Satisfaction with Life Scale, PCL-5 Post Traumatic Stress Disorder checklist, ADHD Symptom Screener, and Sheehan Disability Scale) at baseline, 1.5 (interim) and 3 months after randomization. The study measures, other than the neuro-cognitive assessments, will be completed via REDCap.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a randomized 1:1 block design trial evaluating the effect of a digital cognitive behavioral app versus a drug therapy (amphetamine-dextroamphetamine [Adderall]) on cognitive impairment and other secondary outcomes in subjects with post-COVID symptoms (Long-COVID). The participants will be stratified by depression severity.
| Arm | Type | Receives |
|---|---|---|
| Digital cognitive behavioral intervention- RxWell | Active comparator | Behavioral: Digital cognitive behavioral intervention-RxWellThe mobile app provides users with brief skill building techniques such as relaxation, behavioral activation and exposure, distress tolerance, cognitive reframing, and mindfulness meditation, for anxiety and depression. The content of RxWell was developed based on standard CBT techniques for treating anxiety disorders and depression. The user will have the option to select either the depression or anxiety program, and the coach will have the ability to personalize the program so that the individual can utilize the proper CBT techniques that fits with their presentation. The health coach communicates with RxWell users via asynchronous, secure within app messaging. They reinforce CBT principles, guide users through goal setting, and help users work through challenges and recognize successes. The coaches will also receive individualized cognitive rehabilitation tips from the speech therapist after their appointment with the participant. |
| Stimulant Medication | Active comparator | Drug: Amphetamine-DextroamphetamineThe other intervention is a stimulant medication known to reduce cognitive impairment in other chronic medical conditions, such as Inflammatory Bowel Disease. The Long-COVID psychiatrist will order the medication and the participant will be scheduled for a 6-week research tele visit with the psychiatrist to monitor for any medication side effects. Amphetamine-dextroamphetamine drug dose will be 10mg daily for 12 weeks, and no dose changes will be made. Amphetamine-dextroamphetamine is a Schedule II controlled substance that has a risk for abuse, tolerance, and psychological dependence, which can be associated with severe social disability. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- History of SARS-CoV-2 infection as defined as a positive PCR or home antigen test
- Patients with Long-COVID as defined as COVID symptoms that persist for three months or longer.
- Between the ages of 21 and 65
- Moderate cognitive impairment (MOCA score to meet criteria is < or =18) present for at least 3 months
- Response of "No" to the screening question, "Are you pregnant or do you plan to become pregnant in the next 3 months?"
Key exclusion criteria (9 listed)
- History of dementia, psychosis, mania, addiction or current conditions requiring immediate hospitalization
- Previous adverse or allergic reaction to Adderall or other amphetamines
- Pre-existing cardiac or kidney condition, severe hypertension, glaucoma, advanced arteriosclerosis, hyperthyroidism, and taking an MAOI within the past 14 days
- Current or past substance misuse
- Previous use of RxWell (completed 3 or more techniques)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Digital cognitive behavioral intervention-RxWellRxWell is a coach enhanced digital behavioral health intervention that teaches techniques to help manage emotional distress, which may improve cognitive fog and/or depression. Participants will have access to this app for three months. | Behavioural | Digital cognitive behavioral intervention- RxWell |
| Amphetamine-DextroamphetamineAlso: AdderallParticipants randomized to this arm will be prescribed 10mg of amphetamine-dextroamphetamine to take as needed to help with cognitive fog. Participants in this arm will be contacted at 2 and 6 weeks to assess for any side effects from taking the medication. | Drug | Stimulant Medication |
Primary outcome
Change in Cognitive Impairment - MOCA
Time frame: Compare baseline to 12 weeks
The MOCA is a validated screening tool that provides a total score to assess for mild cognitive impairment.
Change in Cognitive Impairment - BrainCheck
Time frame: Compare baseline to 12 weeks
BrainCheck is an FDA approved validated, automated, remote neurocognitive assessments in multiple domains.
Change in Cognitive Impairment - ImPACT
Time frame: Compare baseline to 12 weeks
ImPACT is an FDA approved computerized neurocognitive concussion assessment tool that provides composite sores to evaluate cognitive abilities.
3 secondary outcomes
Change in Depression - PHQ8
Time frame: Compare baseline up to 12 weeks
Change in Quality of Life - SWLS
Time frame: Compare baseline up to 12 weeks
Change in Disability
Time frame: Compare baseline up to 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Individual participant data will not be shared. Data is shared at the aggregate level.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Szigethy, MD, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Digital cognitive behavioral intervention-RxWell and Amphetamine-Dextroamphetamine in people with Cognitive Impairment and Long COVID, run by Eva Szigethy at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cognitive Impairment - MOCA (time frame: Compare baseline to 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2024.