Randomized, double-blind, placebo-controlled trial of the efficacy and safety of tianeptine in the treatment of covid fog symptoms in patients after COVID-19 with the study of the pathophysiology of the phenomenon using positron emission tomography, biochemical, immunological and electrophysiological parameters (COVMENT).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 Dec 2024 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-510790-19-00

EudraCT number

2022-000893-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Diagnosis, Safety, Therapy

To compare the efficacy of tianeptine versus placebo in the treatment of covid fog symptoms in post COVID-19 patients.
Additional research objective: To determine the pathophysiology of the covid fog phenomenon based on differences in neuropsychological, ENT, neurological, psychiatric, and laboratory test results between post-covid patients with covid fog symptoms and those without covid fog symptoms. To assess changes over time in treatment of neuropsychological, laryngological, neurological, psychiatric, laboratory, and PET-CT findings in patients with covid fog.

Secondary objectives 7

1. To compare other parameters to assess the efficacy of tianeptine versus placebo in the treatment of covid fog symptoms.
2. To assess the effect of treatment on the subjective severity of cognitive difficulties manifested in the subject's daily life.
3. To assess the effect of treatment on subjective feelings of improved functioning and independence.
4. Assessment of the effect of treatment on depressive symptoms.
5. Assessment of the effect of tianeptine treatment on quality of life.
6. Assessment of brain metabolic activity in the course of covid fog as assessed by PET-CT.
7. Comparison of the safety profile of tianeptine treatment versus placebo.

Conditions and MedDRA coding

Covid fog - a dysfunctional condition characterized by slowed thinking, disorientation, difficulty remembering, impaired attention and concentration.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Written informed consent from the patient to participate in the clinical trial.
2. Age ≥ 18 years.
3. History of COVID-19 infection confirmed by a positive SARS-CoV-2 test result by RT-PCR or positive antigen test.
4. Subjective patient-reported cognitive decline after COVID-19 infection at Screening.
5. Cognitive dysfunction found at Screening, defined by the Montreal Scale for the Assessment of Cognitive Function (MoCA) as a score of less than 26.
6. Use of effective contraception by women of childbearing potential.

Exclusion criteria 28

1. Hypersensitivity to tianeptine.
2. Hypersensitivity to fluorodesoxyglucose (FDG).
3. History of allergy to drugs or other substances, which, in the Investigator's opinion, is a contraindication to participation in the study.
4. History of stroke.
5. Ever undergone and planned brain surgery at the time of the study.
6. Previously diagnosed organic damage to the central nervous system.
7. Diagnosed organic mental disorder.
8. Diagnosed bipolar affective disorder.
9. Diagnosed psychotic disorder.
10. Depression with active symptoms requiring initiation or modification of treatment.
11. Diagnosed mental retardation.
12. Bipolar affective disorder in a first-degree relative.
13. Uncontrolled diabetes mellitus.
14. Severe renal failure with eGFR < 30ml/min/1.73 m2.
15. Cirrhosis of liver Severe liver cirrhosis (Child-Pugh class C).
16. Claustrophobia.
17. Diagnosed chronic diseases that significantly worsen the patient's prognosis and quality of life, which, in the Investigator's opinion, may adversely affect the patient's participation in the study.
18. Active or past malignancy within the past 5 years, except for basal cell carcinoma of the skin and cervical cancer in situ in patients who have received radical treatment.
19. Active viral, bacterial, fungal, tuberculous, or parasitic infection.
20. History or presence of other relevant diseases which, in the Investigator's opinion, is a contraindication to participation in the study.
21. Positive pregnancy test performed on women of childbearing potential at screening.
22. Taking medications: (a) Non-selective MAO inhibitors within 14 days prior to screening, (b) Mianserin during screening.
23. Significant difficulty with peripheral venous cannulation.
24. Positive history of alcohol, drug, and psychoactive abuse/dependence.
25. Pregnancy or planning a pregnancy during the study period.
26. Breastfeeding or planning to breastfeed during the study period.
27. Current participation in another clinical trial. Unless taking the investigational product or using the medical device was completed 90 days or 5 x t1/2 before screening.
28. Lack of patient compliance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Improvement in covid fog symptoms at week 16 after randomization defined as a 2 point improvement in MoCA score.

Secondary endpoints 8

1. Complete resolution of covid fog symptoms at week 16 after randomization defined as normalization of MoCA scale score (MoCA = 26 - 30 points).
2. A 10% improvement in raw test scores covering various domains of cognitive functioning at week 16 after randomization: a) CTT, b) COWAT, c) SCWT, d) Repeating Digits from the WAIS-R, e) Digit symbols from WAIS-R.
3. A 10% improvement in ECog-12 test raw scores at week 16 after randomization.
4. Improvement in subjectively assessed depressive symptom severity defined as PHQ score < 5 points at week 16 after randomization.
5. Improvement in subjectively assessed severity of anxiety symptoms defined as GAD-7 score<5 points at 16 weeks after randomization.
6. Improvement in subjectively assessed severity of sleep difficulties defined as AIS score <6 points at 16 weeks after randomization.
7. Improvement in subjectively assessed severity of loneliness defined as SLS score <5 points at 16 weeks after randomization.
8. Reduction in severity or resolution of depressive symptoms as assessed by the MADRS scale. Resolution of symptoms will be defined as a MADRS score < 9 points.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Sponsor organisation

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Address

Ulica Szaserow 128

City

Warsaw

Postcode

04-141

Country

Poland

Scientific contact point

Organisation

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Contact name

Contact point - Covment

Public contact point

Organisation

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy

Contact name

Contact point - Covment

Third parties 3

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications