CLEMASTINE for Schizophrenia

Inclusion criteria

• {"criterion_text":"- Written informed consent obtained from the participant prior to performing any protocol-related procedures, including screening evaluations\n- DSM-V diagnosis of schizophrenia or schizophrenia-spectrum disorder according to MINI interview\n- Age between 18 and 65 years\n- Total Positive and Negative Syndrome Scale (PANSS) score ≤ 75 at V0\n- Stable antipsychotic treatment dose for at least one week prior to inclusion\n- Stable CNS-active treatment substance and dose (e.g. antidepressants and mood stabilizers) for at least one week prior to inclusion\n- 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\n- Female participants with reproductive potential must have a negative serum pregnancy test within seven days prior to randomization\n- 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

• {"criterion_text":"- Patients who are unable to give informed consent\n- Coercive treatment at the time of study inclusion\n- Treatment-naïve schizophrenia defined as cumulative treatment with an antipsychotic agent lifetime for <30 days\n- Insufficient understanding of the German language\n- 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\n- Known clinically relevant CNS disorder(s), such as epilepsy or history of seizures\n- Concomitant use of any other putative remyelinating therapy as determined by investigator\n- Co-occurrent unstable somatic condition\n- Known porphyria\n- Known narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, prostatic hypertrophy with urinary retention and bladder neck obstruction\n- Current treatment with agents with strong anticholinergic properties, such as MAO-inhibitors, opioid antagonists, clozapine at the time of study inclusion\n- 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)\n- 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)\n- Current treatment with macrolide-antibiotics (such as erythromycin, clarithromycine) or azole-type antimycotics\n- Clinically relevant cardiac comorbidities (i.e. Long QT-syndrome)\n- Current hypokalaemia and/or clinically relevant hyponatraemia at screening\n- Patient-reported hereditary galactose-intolerance and/or Lapp lactose-deficiency, lactose intolerance and/or glucose-galactose malabsorption\n- Pregnancy or breast-feeding\n- 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\n- For the optional MRI assessments: potential MRI contraindication(s)"}

Primary endpoints

• {"endpoint_text":"- Absolute change in working memory performance assessed by the nback test (2-back, d-prime) after 90-93 days of treatment.","definition_or_measurement_approach":"Measured by n-back test (2-back level), reported as d-prime; change from baseline (V1.1) to primary outcome visit at 90-93 days (V2)."}
• {"endpoint_text":"- Absolute change in GAF score after 90-93 days of treatment.","definition_or_measurement_approach":"Measured by Global Assessment of Functioning (GAF) score; change from start of intervention (V1.1) to V2 (90-93 days)."}

Secondary endpoints

• {"endpoint_text":"- Change in total PANSS scores at V2 compared to baseline","definition_or_measurement_approach":"Measured by total PANSS score; comparison of V2 to baseline."}
• {"endpoint_text":"- Change in Clinical Global Impression (CGI) rating scale at V2 compared to baseline","definition_or_measurement_approach":"Measured by CGI rating; comparison of V2 to baseline."}
• {"endpoint_text":"- Change in remission criteria (\"Andreasen Remission criteria\") status from V2 compared to baseline","definition_or_measurement_approach":"Assessed using Andreasen Remission criteria; change in remission status at V2 versus baseline."}
• {"endpoint_text":"- Change in GAF and n-back scores (2-back, d-prime) from V3 compared to V2","definition_or_measurement_approach":"Change in GAF and n-back (2-back, d-prime) scores between V3 and V2."}
• {"endpoint_text":"- Change in Calgary Depression Scale for Schizophrenia (CDSS) score at V2 compared to baseline","definition_or_measurement_approach":"Measured by CDSS; comparison of V2 to baseline."}
• {"endpoint_text":"- Change in World Health Organization Quality of Life Brief Version (WHO-QOL-BREF) at V2 compared to baseline","definition_or_measurement_approach":"Measured by WHO-QOL-BREF; comparison of V2 to baseline."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Neurocognitive tests including BACS and TMT A & B; comparison of V2 to baseline across listed domains."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Physical fitness measured by PWC130 (power at HR 130) and power at fixed lactate values; comparison V2 vs baseline."}
• {"endpoint_text":"- Change in weight, waist-to-hip-ratio after 3 months compared to baseline","definition_or_measurement_approach":"Anthropometric measures (weight, waist-to-hip ratio); change at ~3 months versus baseline."}
• {"endpoint_text":"- Change in Physical activity at V2 compared to baseline: Simple Physical Activity Questionnaire (SIMPAQ), actimetry.","definition_or_measurement_approach":"Physical activity assessed by SIMPAQ and actimetry; comparison V2 vs baseline."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"3T MRI modalities (T1-MPRAGE, T2-SPACE, DTI, resting-state MRI, ASL); imaging changes at V2 compared to baseline."}
• {"endpoint_text":"- Change in shortening of P100 latency delay on VEPs at V2 compared to baseline","definition_or_measurement_approach":"Visual evoked potentials (VEPs) P100 latency measurement; change at V2 vs baseline."}
• {"endpoint_text":"- Change in Functional Remission of General Schizophrenia (FROGS) scale at V2 compared to baseline","definition_or_measurement_approach":"Measured by FROGS scale; comparison V2 vs baseline."}
• {"endpoint_text":"- Change in Fatigue Scale for Motor and Cognitive Functions (FSMC) at V2 compared to baseline","definition_or_measurement_approach":"Measured by FSMC; comparison V2 vs baseline."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Psychometric scales IE-4, BRS, ASKU, SSA; comparison V2 vs baseline and correlation analyses with training adherence."}
• {"endpoint_text":"- Change in Exercise Motivations Inventory and Exercise Motives and Gains Inventory (EMI-2) at V2 compared to baseline and associations to training adherence","definition_or_measurement_approach":"Measured by EMI-2 and related inventories; comparison V2 vs baseline and association with adherence."}
• {"endpoint_text":"- Associations between personality factors assessed with the BFI-10 and training adherence","definition_or_measurement_approach":"Personality via BFI-10 correlated with training adherence metrics."}
• {"endpoint_text":"- Change in exploratory rating scales at V3 compared to V2","definition_or_measurement_approach":"Exploratory rating scales assessed at V3 vs V2."}
• {"endpoint_text":"- Change in Andreasen Remission criteria at the optional follow-up visit V3 compared to baseline.","definition_or_measurement_approach":"Andreasen Remission criteria status change at optional V3 vs baseline."}
• {"endpoint_text":"- Side effects and safety endpoints","definition_or_measurement_approach":"Safety and adverse events monitoring; standard safety assessments."}

Germany

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

26-08-2024

Processing Time Days

67

Number Of Sites

2

Number Of Participants

90

Primary sponsor

Full Name

Klinikum der Universitaet Muenchen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany