Investigation of Treating Chronic Fatigue Syndrome After COVID With Pharmacotherapy (Pregabalin) or Complex Rehabilitation

Study Overview
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Brief Summary
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This is a single-center, prospective, randomized, double-blind (pharmacotherapy), placebo-controlled, and comprehensive rehabilitation phase II clinical trial to determine the usefulness of pregabalin in a new indication (post-COVID chronic fatigue syndrome). Patients will be randomized in a 1:1:1:1 ratio to pregabalin (75-300 mg daily in two divided doses), comprehensive rehabilitation with a placebo drug, comprehensive rehabilitation with pregabalin (75-300 mg in two divided doses), or placebo (two divided doses) for 6 months (177-187 days). There will be 4 outpatient visits to the research center and 12 telephone consultations. The procedures and assessments performed as part of the study are listed in the study schedule. It is planned to include 132 patients in the study, which, assuming a 10% level of non-completion of the program, will result in the examination of 120 patients (30 in each arm). Patients will be recruited during an outpatient medical consultation with a general practitioner or neurologist, psychiatrist, psychologist or other specialists, as well as with the use of information materials in the form of leaflets and advertisements on the Internet.

Official Title
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Investigation of Pregabalin Therapy and Complex Rehabilitation in Treating Chronic Fatigue Associated With Post-COVID Syndrome

Conditions
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Chronic Fatigue Syndrome, COVID-19, Long Haul

Intervention / Treatment
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* Drug: Pregabalin
* Behavioral: Independent walking training
* Drug: Placebo
* Behavioral: Gradual movement therapy in the ward
* Behavioral: Telerehabilitation
* Behavioral: Psychotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient correctly gave written informed consent to participate in the study; Men or women between the ages of 18 and 65 inclusive at the time of signing the informed consent; Patient after a minimum of 6 months from the documented detection of SARS-CoV-2 infection (document confirming the history of the disease, including a positive result of the PCR or antigen test, certificate of convalescence; medical documentation confirming the infection; the condition is also considered fulfilled in the case of documented infection asymptomatic); During the screening, the patient meets the criteria for the diagnosis of chronic fatigue syndrome (CFS) according to the National Academy of Medicine (2015); Women: a) incapable of having children (post-menopausal or child-bearing, subjected to permanent sterilization); (b) of childbearing potential with a negative pregnancy test result at screening and using a highly effective method of contraception throughout the IMP use and for 7 days after the last IMP use. The patient agrees to participate in all activities provided for in the study. The patient is able to understand the information presented and give informed consent to participate in the study prior to screening. Exclusion Criteria: Vital functions disorders; Documented hypersensitivity to pregabalin or any of the excipients of the formulation (i.e., lactose); Moderate or severe depression during treatment or present during psychiatric evaluation at baseline; Concurrent treatment with opioids or other antiepileptic drugs (including tramadol, buprenorphine, morphine, oxycodone, gabapentin, duloxetine); Pregnant or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin<br> | Drug: Pregabalin<br>* Pregabalin pharmacotherapy<br>Behavioral: Independent walking training<br>* Independent walking training<br>|
| Experimental: Pregabalin + Rehabilitation<br> | Drug: Pregabalin<br>* Pregabalin pharmacotherapy<br>Behavioral: Independent walking training<br>* Independent walking training<br>Behavioral: Gradual movement therapy in the ward<br>* Gradual movement therapy in the ward<br>Behavioral: Telerehabilitation<br>* Telerehabilitation<br>Behavioral: Psychotherapy<br>* Psychotherapy<br>|
| Experimental: Rehabilitation + Placebo<br> | Behavioral: Independent walking training<br>* Independent walking training<br>Drug: Placebo<br>* Placebo<br>Behavioral: Gradual movement therapy in the ward<br>* Gradual movement therapy in the ward<br>Behavioral: Telerehabilitation<br>* Telerehabilitation<br>Behavioral: Psychotherapy<br>* Psychotherapy<br>|
| Placebo Comparator: Placebo<br> | Behavioral: Independent walking training<br>* Independent walking training<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fatigue intensity expressed as a difference in Multidimensional Fatigue Inventory-20 (MFI-20) score | Change in fatigue intensity expressed as a difference in Multidimensional Fatigue Inventory-20 (MFI-20) score at 3 and 6 months of the study relative to the baseline score | 3 months and 6 months | 
| Walking distance as a difference in score from the 6 Minute Walking Test | Walking distance as a difference in score from the 6 Minute Walking Test at 3 and 6 months compared to baseline | 3 months and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the level of satisfaction with life expressed in the form of the result of the Satisfaction with Life Scale (Juczyński) | Change in the level of satisfaction with life expressed in the form of the result of the Satisfaction with Life Scale (Juczyński) in the 3rd and 6th month of the study in relation to the result on the day of the study | 3 months and 6 months | 
| Change in the result obtained in the Beck Depression Inventory (BDIII) study | Change in the result obtained in the Beck Depression Inventory (BDIII) study in the 3rd and 6th month of the study in relation to the result on the day of the study commencement. | 3 months and 6 months | 
| Change in the result obtained in the anxiety test - State and Trait Anxiety Inventory (STAI) | Change in the result obtained in the anxiety test - State and Trait Anxiety Inventory (STAI) in the 3rd and 6th month of the study in relation to the result on the day of the study commencement. | 3 months and 6 months | 
| Change in the degree of acceptance of the disease assessed by the Acceptance of Illness Scale (Juczyński) i | Change in the degree of acceptance of the disease assessed by the Acceptance of Illness Scale (Juczyński) in the 3rd and 6th month of the study in relation to the result on the day of starting the study | 3 months and 6 months | 
| Change in the result of the CCT test | Change in the result of the CCT test in the 3rd and 6th month of the study compared to the result on the day of starting the study. | 3 months and 6 months | 
| Change in neuropsychological assessment expressed by the change in the result of the Wisconsin Card Sorting Test (WCST) | Change in neuropsychological assessment expressed by the change in the result of the Wisconsin Card Sorting Test (WCST) in the 3rd and 6th month of the study compared to the result on the day of the study commencement. | 3 months and 6 months | 
| Change in the result of the RFFT test | Change in the result of the RFFT test in the 3rd and 6th month of the study compared to the result on the day of starting the study. | 3 months and 6 months | 
| Change in the WAIS-R intelligence test result | Change in the WAIS-R intelligence test result in the 3rd and 6th month of the study in relation to the result on the day of the study commencement | 3 months and 6 months | 
| Change in reaction time expressed by the Stroop interference test | Change in reaction time expressed by the Stroop interference test in the 3rd and 6th month of the study compared to the result on the day of the study start. | 3 months and 6 months | 
| Change in the assessment of the quality of gait | Change in the assessment of the quality of gait in the 3rd and 6th month of the study in relation to the result on the day of the beginning of the study | 3 months and 6 months | 
| Change in walking speed | Change in walking speed in the 3rd and 6th month of the study in relation to the result on the day of the study. | 3 months and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic fatigue syndrome, associated with post-COVID syndrome