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

Exclusion Criteria

• •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 lactosedeficiency, 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)