Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS)

NCT05986422 | Terminated Phase 2 DMC

• 2 other identifiers: PoCoVIT01EP2201
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial aims to learn about the therapeutic value of Methylprednisolone, a well-known immunosuppressant, on cognitive deficits in patients with post-COVID-19 syndrome (PCS). The main questions it aims to answer are: 1) Does Methylprednisolone improve memory function in PCS patients compared to placebo? 2) Does Methylprednisolone improve other patient centered outcomes in PCS patients such as fatigue, mood and quality of life compared to placebo? 3)What are the side effects of Methylprednisolone in this patient population, and how common are they? Participants in this study will be patients with PCS and cognitive deficits, who will be asked to participate for 52 weeks. They will be randomly assigned to one of two groups: One group will receive Methylprednisolone once daily for six weeks, with a dosage reduction after week 4. The other group will receive a matching placebo once daily for six weeks, following the same titration regimen to ensure blinding. Participants will attend outpatient follow-up visits in weeks 8 and 20, with a final telephone follow-up after 52 weeks. Clinical examinations and safety monitoring will be conducted during the treatment phase. This study's results may help develop more effective therapies for this condition.

Conditions

Post-COVID-19 Syndrome

Keywords

Long COVID; Cognitive deficits

Outcome Measures

Primary Outcomes (1)

• Improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ)

  The MMQ is a participant-reported measure of memory satisfaction. It consists of three scales measuring separate aspects of metamemory including memory satisfaction, memory ability, and memory strategy. For memory satisfaction, eighteen items are rated on a 5-point Likert scale based on the test taker's experience over the previous two weeks.The score range is 0 to 72, with higher scores indicating a higher degree of satisfaction. A change of 13 points is commonly rated as clinically significant change. In this study, intra-patient change in MMQ subdomain memory satisfaction by ≥15 points from baseline to week 8 will be interpreted as meaningful improvement.

  8 weeks after first IMP intake

Secondary Outcomes (9)

• Long-term improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ)

  20 and 52 weeks after first IMP intake

• Improvement in memory ability and memory strategy as measured by the Multifactorial Memory Questionnaire

  8 and 20 weeks after first IMP intake

• Improvement in neurocognitive functions as measured by the Montreal Cognitive Assessment (MoCA)

  8 and 20 weeks after first IMP intake

• Improvement in neurocognitive functions as measured by the symbol digit modalities test (SDMT)

  8 and 20 weeks after first IMP intake

• Improvement in quality of life (QoL) as measured by the PROMIS questionnaire

  8, 20, and 52 weeks after first IMP intake

Study Arms (2)

Methylprednisolone

ACTIVE COMPARATOR

Tested IMP: Methylprednisolone (film-coated tablet). Authorization status: Not authorized in this targeted therapeutic indication; methylprednisolone is authorized for treatment of multiple autoimmune diseases. The tablets being administered in this trial are an official trade product provided by the marketing authorization holder JenaPharm. Administration: Tablet containing 16 mg/tablet will be administered orally and according to bodyweight groups. Treatment period comprises 6 weeks of blinded daily IMP (investigational medicinal product) intake (verum or placebo) and 6 weeks of unblinded daily intake of Methylprednisolone. The general IMP titration regimen was investigated and proven to be safe in patients with cerebral vasculitis (Schirmer et al., 2020).

Drug: Methylprednisolone

Placebo

PLACEBO COMPARATOR

Comparator IMP: Placebo (film-coated tablet). Authorization status: Not authorized. To ensure identical conditions with the verum (Methylprednisolone), we will use placebo tablets of the same color and size in identical tablet packages for both the verum and placebo. Administration: Tablets (7 mm) will be administered orally and according to bodyweight groups. To achieve consistent conditions with the verum, titration will be conducted in a manner similar to the tested IMP (Methylprednisolone). Treatment period comprises 6 weeks of blinded daily IMP intake (placebo or verum) and 6 weeks of unblinded daily intake of Methylprednisolone.

Drug: Methylprednisolone

Interventions

Methylprednisolone DRUG

The treatment period consists of six weeks of daily intake of either Methylprednisolone or placebo (depending on randomization), followed by an additional six weeks of daily intake of open-label Methylprednisolone. During the study, follow-up assessments will be conducted at two points: at week 8 and week 20 from the start of each treatment phase.

Methylprednisolone; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of confirmed (PCR or serology) SARS-CoV-2 infection according to WHO criteria
• Ongoing symptoms of PCS for ≥ 3 months
• Self-reported cognitive deficits at screening
• Male or female adult who is 18 years or older at the time of informed consent
• Subject is willing, understanding and able to provide informed consent
• Signed informed consent prior to initiation of any trial related measure
• For female subject or divers subjects:
• Confirmed post-menopausal state, defined as amenorrhea for at least 12 months, or
• If being of childbearing potential:
• Practicing a highly effective birth control method (failure rate of less than 1%)

You may not qualify if:

• Any ongoing central nervous system disease
• Any major psychiatric disease within the last 10 years
• Previous medical history of gastric ulcer, osteoporosis and/or previous vertebral fractures, rheumatological disease or metabolic disease including diabetes mellitus
• Ongoing immunosuppressive therapy
• Patient is pregnant or breastfeeding at screening
• MMQ memory satisfaction subdomain \>50 points at Screening
• Current malignant disease (including space-occupying brain tumors)
• Body weight \<45kg
• Severe lactose intolerance
• Participation in another clinical interventional trial within the last 3 months or five half- lives of the other trial's IMP, if longer than 6 months previous to informed consent
• Patient is institutionalized by order of court or public authority
• Patient who might be dependent on the sponsor, the investigator or the trial site
• Place of living does not allow the subject to attend the planned study visits
• Other conditions that are likely to affect to safety of the study treatment (e.g., severely impaired immune status)

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, 10117, Germany

Location

Related Publications (3)

• Schirmer JH, Aries PM, Balzer K, Berlit P, Bley TA, Buttgereit F, Czihal M, Dechant C, Dejaco C, Garske U, Henes J, Holle JU, Holl-Ulrich K, Lamprecht P, Nolle B, Moosig F, Rech J, Scheuermann K, Schmalzing M, Schmidt WA, Schneider M, Schulze-Koops H, Venhoff N, Villiger PM, Witte T, Zanker M, Hellmich B. [S2k guidelines: management of large-vessel vasculitis]. Z Rheumatol. 2020 Nov;79(Suppl 3):67-95. doi: 10.1007/s00393-020-00893-1. No abstract available. German.

  PMID: 33156399 BACKGROUND

• Boesl F, Audebert H, Endres M, Pruss H, Franke C. A Neurological Outpatient Clinic for Patients With Post-COVID-19 Syndrome - A Report on the Clinical Presentations of the First 100 Patients. Front Neurol. 2021 Sep 16;12:738405. doi: 10.3389/fneur.2021.738405. eCollection 2021.

  PMID: 34603189 BACKGROUND

• Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, Rodrigues NB, Subramaniapillai M, Di Vincenzo JD, Cao B, Lin K, Mansur RB, Ho RC, Rosenblat JD, Miskowiak KW, Vinberg M, Maletic V, McIntyre RS. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022 Mar;101:93-135. doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29.

  PMID: 34973396 BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Cognition Disorders

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Heinrich Audebert, Prof., MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director of the Department of Neurology with Experimental Neurology at Charite Campus Benjamin Franklin

Model Details: Double-blind, randomized, placebo-controlled trial.

Study Record Dates

• First Submitted: August 9, 2023
• First Posted: August 14, 2023
• Study Start: October 1, 2023
• Primary Completion: March 14, 2025
• Study Completion: February 19, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

DE (1)