Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity
- Conditions
- F20Schizophrenia
- Registration Number
- DRKS00032316
- Lead Sponsor
- Klinikum der Universität München
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 90
• Written informed consent obtained from the participant prior to performing any protocol-related procedures, including screening evaluations
• A DSM-V diagnosis of schizophrenia or schizophrenia-spectrum disorder according to MINI interview
• Age between 18 and 65 years
• Total Positive and Negative Syndrome Scale (PANSS) score = 75 at V0
• Stable antipsychotic treatment dose for at least one week prior to inclusion
• Stable CNS-active treatment substance and dose (e.g. antidepressants and mood stabilizers) for at least one week prior to inclusion
• Female participants with reproductive potential must have a negative pregnancy test using a pregnancy test strip as part of the screening visit
• Female participants with reproductive potential must have a negative serum pregnancy test within seven days prior to randomization
• 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
• A woman who is not capable of bearing a child is defined as follows: post-menopausal (12 months natural (spontaneous) amenorrhea or 6 months spontaneous amenorrhea with serum-FSH-values (follicle-stimulating hormone) of >40 mIU/mL); 6 weeks after a bilateral ovariectomy with or without hysterectomy or sterilization by means of tubal ligation
• A woman capable of bearing child is defined as follows: a woman who is physiologically capable of becoming pregnant, including women whose occupation, lifestyle or sexual orientation exclude sexual intercourse with a male partner and women whose partners have been sterilized by vasectomy or other measures.
• Medically-approved acceptable methods of contraception with a low failure rate (i.e. less than 1% per year) when used consistently and correct can include the following: hormonal contraceptives, intrauterine device and double barrier method. Acceptable preventive measures can include total abstinence at the discretion of the investigator, in cases where compliance is ensured because of the study participant’s age, occupation, lifestyle or sexual orientation. Periodical abstinence (e.g. calendar, ovulation, symptothermal methods or abstinence until the 4th day after the ovulation) as well as coitus interruptus are not acceptable methods of contraception.
A reliable method of contraception (CTFG guideline) must be used for the entire duration of the study.
• Patients who are unable to give informed consent
• Coercive treatment at the time of study inclusion
• Treatment-naïve schizophrenia defined as cumulative treatment with an antipsychotic agent lifetime for <30 days
• Insufficient understanding of the German language
• 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
• Known clinically relevant CNS disorder(s), such as epilepsy or history of seizures
• Concomitant use of any other putative remyelinating therapy as determined by investigator
• Co-occurrent unstable somatic condition
• Known porphyria
• Known narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, prostatic hypertrophy with urinary retention and bladder neck obstruction
• Current treatment with agents with strong anticholinergic properties, such as MAO-inhibitors, opioid antagonists, clozapine at the time of study inclusion
• 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)
• 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)
• Current treatment with macrolide-antibiotics (such as erythromycin, clarithromycine) or azole-type antimycotics
• Clinically relevant cardiac comorbidities (i.e. Long QT-syndrome)
• Current hypokalaemia and/or clinically relevant hyponatraemia at screening
• Patient-reported hereditary galactose-intolerance and/or Lapp lactose-deficiency, lactose intolerance and/or glucose-galactose malabsorption
• Pregnancy or breast-feeding
• 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.
• For the optional MRI assessments: potential MRI contraindication(s)
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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). <br>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 Outcome Measures
Name Time Method Secondary objectives include differences in side effects, symptom severity (PANSS total, CGI), remission status and safety measures at V2, change in GAF and n-back scores from V3 compared to V2, exploratory objectives include changes in other cognitive functions, depressive symptoms, quality of life, metabolic parameters (weight, hip-to-waist-ratio), physical fitness, relationship between personality-associated characteristics, motivational aspects and training adherence, changes in multimodal MRI parameters and shortening of P100 latency delay on visual evoked potentials (VEPs) at V2 compared to baseline (V1.1).