Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity (OligoTreat)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Klinikum der Universitaet Muenchen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

26 Feb 2024 → ongoing

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514457-30-00

EudraCT number

2022-000054-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective 1 is the change in Global Assessment of Functioning (GAF) scores from the start of the intervention period (V1.1) to primary outcome visit after 90-93 days of treatment (V2).
The primary objective 2 is the change in working memory performance assessed by the n-back test (2-back level, d-prime) from V1.1 to V2.

Secondary objectives 4

1. Change in total PANSS scores at V2 compared to baseline
2. Change in Clinical Global Impression (CGI) rating scale at V2 compared to baseline
3. Change in remission criteria ("Andreasen Remission criteria") status from V2 compared to baseline
4. Change in GAF and n-back scores (2-back, d-prime) from V3 compared to V2

Conditions and MedDRA coding

Schizophrenia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Written informed consent obtained from the participant prior to performing any protocol-related procedures, including screening evaluations
2. DSM-V diagnosis of schizophrenia or schizophrenia-spectrum disorder according to MINI interview
3. Age between 18 and 65 years
4. Total Positive and Negative Syndrome Scale (PANSS) score ≤ 75 at V0
5. Stable antipsychotic treatment dose for at least one week prior to inclusion
6. Stable CNS-active treatment substance and dose (e.g. antidepressants and mood stabilizers) for at least one week prior to inclusion
7. Female participants with reproductive potential must have a negative beta-HCG serum pregnancy test using a pregnancy test strip as part of the screening visit
8. Female participants with reproductive potential must have a negative serum pregnancy test within seven days prior to randomization
9. Male participants and female participants who are not capable of bearing children or who use a method of contraception that is medically approved by the health authority of the respective country at screening

Exclusion criteria 20

1. Patients who are unable to give informed consent
2. Coercive treatment at the time of study inclusion
3. Treatment-naïve schizophrenia defined as cumulative treatment with an antipsychotic agent lifetime for <30 days
4. Insufficient understanding of the German language
5. Patients with primary active (moderate or severe) substance use disorder (other than nicotine) according to MINI interview (DSM-V): patients fulfilling early (>3 months) or sustained (>12 months) remission criteria and/or with low severity of substance use disorder according to MINI are eligible for the study
6. Known clinically relevant CNS disorder(s), such as epilepsy or history of seizures
7. Concomitant use of any other putative remyelinating therapy as determined by investigator
8. Co-occurrent unstable somatic condition
9. Known porphyria
10. Known narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, prostatic hypertrophy with urinary retention and bladder neck obstruction
11. Current treatment with agents with strong anticholinergic properties, such as MAO-inhibitors, opioid antagonists, clozapine at the time of study inclusion
12. Known intolerance, allergy/contraindications to one of the study drugs or any of the excipients or other agents with similar chemical properties as the study drugs (such as other arylalkylamine antihistamines)
13. Clinically relevant liver and/or renal impairment (serum creatinine >1.5mg/dl or eGFR<30 ml/min/1.73 m2 at screening, AST or ALT > 2- times the upper limit of normal at screening)
14. Current treatment with macrolide-antibiotics (such as erythromycin, clarithromycine) or azole-type antimycotics
15. Clinically relevant cardiac comorbidities (i.e. Long QT-syndrome)
16. Current hypokalaemia and/or clinically relevant hyponatraemia at screening
17. Patient-reported hereditary galactose-intolerance and/or Lapp lactose-deficiency, lactose intolerance and/or glucose-galactose malabsorption
18. Pregnancy or breast-feeding
19. Concurrent enrolment in another clinical trial where the participant is receiving an IMP or participation in another clinical trial with IMP during the last 30 days before inclusion or 7 half-lives of previously used IMP, whichever is longer
20. For the optional MRI assessments: potential MRI contraindication(s)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Absolute change in working memory performance assessed by the nback test (2-back, d-prime) after 90-93 days of treatment.
2. Absolute change in GAF score after 90-93 days of treatment.

Secondary endpoints 20

1. Change in total PANSS scores at V2 compared to baseline
2. Change in Clinical Global Impression (CGI) rating scale at V2 compared to baseline
3. Change in remission criteria ("Andreasen Remission criteria") status from V2 compared to baseline
4. Change in GAF and n-back scores (2-back, d-prime) from V3 compared to V2
5. Change in Calgary Depression Scale for Schizophrenia (CDSS) score at V2 compared to baseline
6. Change in World Health Organization Quality of Life Brief Version (WHO-QOL-BREF) at V2 compared to baseline
7. Change in verbal memory and fluency, motor speed, attention, speed of information processing, working memory, executive functions, and global cognition according to the Brief Assessment of Cognition in Schizophrenia (BACS) and change in attention span and executive functions in the Trail Making Test (TMT) A & B at V2 compared to baseline
8. Change in Physical fitness at V2 compared to baseline: Physical working capacity (PWC130: power [W] at a heart rate of 130 beats per minute, power [W] at fixed values of lactate concentrations)
9. Change in weight, waist-to-hip-ratio after 3 months compared to baseline
10. Change in Physical activity at V2 compared to baseline: Simple Physical Activity Questionnaire (SIMPAQ), actimetry.
11. Change in 3T MRI at V2 (day 90-93): structural MRI (T1-MPRAGE, T2- SPACE), DTI, resting-state MRI and ASL, all compared to baseline
12. Change in shortening of P100 latency delay on VEPs at V2 compared to baseline
13. Change in Functional Remission of General Schizophrenia (FROGS) scale at V2 compared to baseline
14. Change in Fatigue Scale for Motor and Cognitive Functions (FSMC) at V2 compared to baseline
15. Change in Internal-External Locus of Control Scale (IE-4), Resilience (BRS), Selfefficacy (ASKU) and exercise-related selfefficacy (SSA) at V2 compared to baseline and associations to training adherence
16. Change in Exercise Motivations Inventory and Exercise Motives and Gains Inventory (EMI-2) at V2 compared to baseline and associations to training adherence
17. Associations between personality factors assessed with the BFI-10 and training adherence
18. Change in exploratory rating scales at V3 compared to V2
19. Change in Andreasen Remission criteria at the optional follow-up visit V3 compared to baseline.
20. Side effects and safety endpoints

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum der Universitaet Muenchen AöR

Sponsor organisation

Klinikum der Universitaet Muenchen AöR

Address

Nussbaumstrasse 7, Ludwigsvorstadt-Isarvorstadt Ludwigsvorstadt-Isarvorstadt

City

Munich

Postcode

80336

Country

Germany

Scientific contact point

Organisation

Klinikum der Universitaet Muenchen AöR

Contact name

Prof. Dr. med. Peter Falkai

Public contact point

Organisation

Klinikum der Universitaet Muenchen AöR

Contact name

Prof. Dr. med. Peter Falkai

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 6 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