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

NCT ID: NCT05986422

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 418 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2025-12-31

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.

Detailed Description

Around 10-40% of mild COVID-19 patients experience persisting or new symptoms known as post-COVID-19 syndrome (PCS). Neurological symptoms, particularly cognitive deficits and fatigue, are common in PCS, with a higher prevalence in female patients (Boesl et al., 2021; Ceban et al., 2022). The underlying causes of PCS remain unclear, but some evidence suggests autoimmune mechanisms may play a role. Currently, there are no proven treatments for PCS, leading to a need for effective therapies. This randomized controlled trial (RCT) aims to investigate the impact of methylprednisolone, a generally well-tolerated and affordable drug, on cognitive deficits in PCS patients with suspected autoimmune involvement.

The objective is to demonstrate improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ) in patients with post-COVID-19 syndrome treated with Methylprednisolone compared with placebo. Methylprednisolone is a well-known immunosuppressant used for multiple diseases of (suspected) autoimmune etiology.

This is a two-arm, double-blind, randomized, placebo-controlled trial evaluating the effects of Methylprednisolone versus placebo in patients with post-COVID-19 syndrome (PCS) and cognitive deficits. The study spans 52 weeks, and participants will be stratified based on age, sex, and cognitive screening using the Montreal Cognitive Assessment Scale (MoCA). They will be randomly assigned in a 1:1 ratio to receive either Methylprednisolone (including a tapering phase) or placebo for 6 weeks, followed by an additional 6 weeks of open treatment phase with Methylprednisolone after a 6-weeks treatment pause. During the study, follow-up visits will be conducted as outpatient visits in weeks 8 and 20, with a final telephone follow-up after 52 weeks. The screening and baseline examinations will involve recording of medical history, checking inclusion and exclusion criteria, and conducting clinical examinations. The intervention group will receive approximately 1mg/kg body weight oral Methylprednisolone once daily for 6 weeks, with dosage reduction after week 4. The other group will receive a matching placebo once daily for 6 weeks, following the same titration regimen to maintain blinding. The starting dose for both interventions will be Methylprednisolone at approximately 1 mg/kg body weight or matching placebo once per day. Throughout the treatment phase, all participants will undergo safety and monitoring examinations.

This clinical trial is of significant importance as it has the potential to benefit individuals with post-COVID-19 syndrome (PCS) by exploring the effects of Methylprednisolone on cognitive impairment and fatigue. Additionally, it may provide crucial insights into PCS's pathophysiological processes, leading to the development of more effective therapies and improved patient outcomes.

Conditions

Post-COVID-19 Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Methylprednisolone

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).

Group Type: ACTIVE_COMPARATOR

Methylprednisolone

Intervention Type: 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.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Methylprednisolone

Intervention Type: 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.

Interventions

Methylprednisolone

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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:

1. Confirmed post-menopausal state, defined as amenorrhea for at least 12 months, or

2. If being of childbearing potential:

1. Negative highly sensitive urine or serum pregnancy test before inclusion, and

2. Practicing a highly effective birth control method (failure rate of less than 1%)

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Heinrich J Audebert

Deputy Director of the Department of Neurology with Experimental Neurology at Charite Campus Benjamin Franklin

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Heinrich Audebert, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Locations

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Christiana Franke, MD

Role: CONTACT

christiana.franke@charite.de

+49 30 450 560883

Heinrich Audebert, Prof., MD

Role: CONTACT

heinrich.audebert@charite.de

+49 30 450 560832

Facility Contacts

Christiana Franke, MD

Role: primary

christiana.franke@charite.de

+49 30 450 560883

References

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.

Reference Type: BACKGROUND

PMID: 33156399 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34603189 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34973396 (View on PubMed)

Other Identifiers

01EP2201

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PoCoVIT

Identifier Type: -

Identifier Source: org_study_id