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

Inclusion Criteria: * • 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 EudraCT Number: 2022-000054-28 Confidential OligoTreat Study Protocol Version 2.0 06.09.2023 9 of 62 * 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 beta- HCG serum pregnancy test 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 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)