Clinical trial NCT05986422: Methylprednisolone in Patients with Cognitive Deficits in Post-COVID-19 Syndrome (PCS)
Official title: Phase 2a, Double-blind, Randomized, Placebo-controlled Trial of Methylprednisolone Versus Placebo in Patients with Cognitive Deficits in Post-COVID-19 Syndrome (PCS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Post-COVID-19 Syndrome
Keywords: Long COVID
Cognitive deficits
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 418
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, placebo-controlled trial.
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ)
timeFrame: 8 weeks after first IMP intake
Secondary outcomes:
measure: Long-term improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ)
timeFrame: 20 and 52 weeks after first IMP intake
measure: Improvement in memory ability and memory strategy as measured by the Multifactorial Memory Questionnaire
timeFrame: 8 and 20 weeks after first IMP intake
measure: Improvement in neurocognitive functions as measured by the Montreal Cognitive Assessment (MoCA)
timeFrame: 8 and 20 weeks after first IMP intake
measure: Improvement in neurocognitive functions as measured by the symbol digit modalities test (SDMT)
timeFrame: 8 and 20 weeks after first IMP intake
measure: Improvement in quality of life (QoL) as measured by the PROMIS questionnaire
timeFrame: 8, 20, and 52 weeks after first IMP intake
measure: Improvement in physical and mental fatigue as measured by the Chalder Fatigue Scale
timeFrame: 8, 20, and 52 weeks after first IMP intake
measure: Improvement in fatigue as measured by the Fatigue Severity Score (FSS)
timeFrame: 8, 20, and 52 weeks after first IMP intake
measure: Improvement in mood as measured by the Becks Depression Inventory (BDI-II)
timeFrame: 8, 20, and 52 weeks after first IMP intake
measure: Difference of occurring AE and SAE comparing Methyprednisolone with placebo (IMP safety).
timeFrame: 8 and 20 weeks after first IMP intake
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Heinrich Audebert, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.