Rimonabant for Cognitive Impairment in People With Post-COVID-19 Syndrome (RIMOCOVID-1)

Participants receive rimonabant 5 mg orally once daily for 90 days.

Rimonabant 2.5 mg tablets. Two tablets are taken together orally once a day in fasted conditions, providing a total daily dose of 5 mg. Treatment duration is 90 days.

Participants receive matching placebo orally once daily for 90 days.

Placebo tablets matching the appearance of the rimonabant tablets. Two tablets are taken together orally once daily in fasted conditions. Treatment duration is 90 days.

The SDMT assesses cognitive processing speed using the validated Spanish version of the test. Participants must match symbols to their corresponding numbers within 90 seconds. The raw score is the number of correct responses, ranging from 0 to 110; higher scores indicate better performance. Age- and education-adjusted scores are calculated using Spanish normative data.

The Borg CR10 Scale assesses perceived exertion after the 6MWT. Scores range from 0 (no exertion) to 10 (maximal exertion). Higher scores indicate greater perceived exertion.

The Fatigue Severity Scale assesses fatigue severity and its impact on daily functioning during the preceding week. It consists of nine items rated from 1 to 7. The mean score ranges from 1 to 7. Higher scores indicate greater fatigue severity.

The TAVEC assesses verbal learning and episodic memory through repeated word-list learning, interference, delayed recall, and recognition tasks. Age-adjusted standardized scores characterize verbal learning and memory performance.

The Frontal Assessment Battery assesses executive function through six subtests. The total score ranges from 0 to 18. Higher scores indicate better executive functioning.

The MOS Sleep Scale assesses sleep quality and sleep-related problems during the preceding four weeks. Scaled domain scores range from 0 to 100. Higher sleep-problem scores indicate worse sleep, whereas higher sleep-adequacy scores indicate better sleep adequacy.

The Brain Fog Scale assesses subjective cognitive symptoms, including mental clouding, slowed thinking, and difficulties with concentration and attention. Higher total scores indicate greater perceived cognitive impairment.

The SART assesses sustained attention and inhibitory control through a computerized go/no-go task. Participants respond to frequent non-target digits and withhold responses to the infrequent target digit 3. Recorded variables include reaction time, commission errors (responses to the target), and omission errors (missed responses to non-targets). Reaction time reflects response speed, while higher error counts indicate poorer sustained attention or inhibitory control.

The Stroop Test assesses cognitive inhibition and processing speed through congruent and incongruent conditions. Recorded variables include reaction time and the number of errors in each condition. Longer reaction times indicate slower performance, while higher error counts indicate poorer accuracy.

The Beck Depression Inventory-II assesses depressive symptom severity over the preceding two weeks. It consists of 21 items scored from 0 to 3. The total score ranges from 0 to 63. Higher scores indicate more severe depressive symptoms.

The Hospital Anxiety and Depression Scale assesses symptoms of anxiety and depression over the preceding week. It consists of 14 items scored from 0 to 3. The combined total score ranges from 0 to 42. Higher scores indicate greater symptom severity.

The Ten-Meter Walk Test assesses walking performance by measuring the time required to walk 10 meters, expressed in seconds. Shorter completion times indicate faster walking performance.

The Timed Up and Go Test assesses functional mobility by measuring the time required to rise from a chair, walk three meters, turn, return to the chair, and sit down. Completion time is expressed in seconds. Shorter times indicate better functional mobility.

The Patient Global Impression of Change assesses the participant's overall perception of improvement or worsening compared with their condition at baseline. Participants report whether their overall condition has improved, remained unchanged, or worsened.

The EQ-5D-5L assesses health-related quality of life across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels, from no problems to extreme problems or inability to perform the activity. Higher dimension levels indicate greater health problems.

The Overall Mood Scale assesses the participant's overall mood using a numerical rating from 0 (very poor mood) to 10 (excellent mood). Participants complete the rating at baseline and weekly in their diary. Higher scores indicate better mood.

Safety is assessed by the number of participants experiencing at least one adverse event beginning after the first administration of study medication. Events are classified by severity and relationship to study medication. Serious adverse events, adverse events of special interest, and events leading to withdrawal are summarized separately.

The VAS assesses self-perceived health using a 10-cm horizontal line. The left end represents very poor health, and the right end represents very good health. Participants mark the point that best reflects their perceived health status. Positions closer to the right end indicate better perceived health.

Cognitive fatigue is assessed using the Cognitive Fatigue Index derived from the SDMT (CFI-SDMT), which reflects the relative change in correct responses between the initial and final 30-second intervals of the 90-second test. Negative values indicate declining performance. Measures include the CFI-SDMT score and the percentage of participants presenting cognitive fatigue, defined as a decline in performance of more than 10% between these intervals.

Responder rates are reported separately as the percentage of participants achieving an increase of at least 4 points in the SDMT total raw score from baseline and the percentage achieving an improvement of at least 10% in the CFI-SDMT from baseline.