MIRTAZAPINE for Rett syndrome

Inclusion criteria

• {"criterion_text":"- Female patients aged > 5 years\n- Body weight > 10 kg\n- Diagnosis of RTT confirmed by MECP2 gene mutation\n- Respiratory dysfunction (at least one of the following): periodic apnoea, intermittent hyperventilation, breath holding, swallowing of air, forced expulsion of air and/or saliva\n- Ten or more episodes per day of respiratory dysfunction during wakefulness in the week preceding the screening visit (reported by the caregiver)\n- Stable medication regimen for 4 weeks prior to the start of the study\n- Females of childbearing age only with negative pregnancy test\n- Written consent signed by parent/legal guardian/representative prior to screening visit\n- The patient is cooperative, willing and able to complete the study with caregiver assistance\n- The caregiver is able to understand the purpose of the protocol and to cooperate in the study"}

Exclusion criteria

• {"criterion_text":"- They are participating in another investigational clinical trial\n- Hypersensitivity to MTZ\n- Clinically significant (as determined by the investigator) cardiovascular, respiratory, gastrointestinal, renal, hepatic, haematological pathologies or other pathologies, in addition to those directly related to RTT. In particular, patients with the following parameters will be excluded: leucocyte count is < 4000/mm2; neutrophil count is < 2000/mm3; hyponatremia (< 125 mmol/L); renal dysfunction (creatinine > 2 X ULN), hepatic dysfunction (AST, ALT, bilirubin > 2 X ULN); or if severe diabetes mellitus is present\n- QTcF interval at ECG > 450 msec\n- Scheduled surgery during the study\n- Severe diabetes mellitus (hyperglycaemia with values above 250/300 mg/dL)\n- Pregnancy, breastfeeding\n- Evidence of clinically significant malnutrition with BMI (or BMI) (kg/m2) <13"}

Primary endpoints

• {"endpoint_text":"- The rating scale used is the Motor-Behavior Assessment Scale (MBAS). The drug will be considered effective if the treatment decreases the Motor-Behavior Assessment Scale (MBAS) score (maximum score=68) by at least 8.5 points (12.5%) compared to baseline.","definition_or_measurement_approach":"Motor-Behavior Assessment Scale (MBAS); effectiveness defined as a reduction of MBAS score by at least 8.5 points (12.5%) compared to baseline."}

Secondary endpoints

• {"endpoint_text":"- The drug will be considered effective if the treatment reduces the overall Anxiety, Depression, and Mood Scale (ADAMS) score (maximum score=84) by at least 10.6 points (12.5%) and reduces the overall Rett Syndrome Behaviour Questionnaire (RSBQ) score by at least 11.25 points (12.5%)","definition_or_measurement_approach":"ADAMS and RSBQ scales; effectiveness thresholds: ADAMS reduction ≥10.6 points (12.5%); RSBQ reduction ≥11.25 points (12.5%)."}
• {"endpoint_text":"- The drug will be considered effective if the treatment improves the measurements obtained from the medical devices for remote sensing (Youcare Smart T-shirt and the Actigraphy), and the Sleep disturbances scale for children (SDSC) scores by at least 20% compared to the initial value","definition_or_measurement_approach":"Remote-sensing device measurements (Youcare Smart T-shirt, Actigraphy) and SDSC; effectiveness defined as ≥20% improvement from baseline."}
• {"endpoint_text":"- The drug will be considered effective if the Purposeful Hand Function scale (PHF) score increases at least 2 points above the baseline score.","definition_or_measurement_approach":"Purposeful Hand Function (PHF) scale; effectiveness defined as increase of ≥2 points from baseline."}
• {"endpoint_text":"- The drug will be considered effective if the Clinical Global Impression of Change scale (CGI-C) has a score decrease at least 1 point","definition_or_measurement_approach":"Clinical Global Impression of Change (CGI-C); effectiveness defined as decrease of ≥1 point."}
• {"endpoint_text":"- The drug will be considered effective if the Rett Syndrome Severity Scale (RCSS) scores decrease at least 3%, i.e. by 2 points","definition_or_measurement_approach":"Rett Syndrome Severity Scale (RCSS); effectiveness defined as decrease of ≥3% (≈2 points)."}
• {"endpoint_text":"- The assessment will be performed through measurements of thoracic and abdominal respiratory movements, airflow, arterial oxyhaemoglobin saturation (HbSaO2), heart rate and posture","definition_or_measurement_approach":"Respiratory function measurements: thoracic/abdominal movements, airflow, HbSaO2, heart rate, posture (device-based assessments)."}
• {"endpoint_text":"- The rating scale used will be the Parenting Stress Index (PSI-SF). An improvement in parental stress will be considered as such, if the Parenting Stress Index (PSI-SF) shows a reduction of at least 20%","definition_or_measurement_approach":"Parenting Stress Index (PSI-SF); effectiveness defined as ≥20% reduction from baseline."}
• {"endpoint_text":"- The effectiveness of the drug will be assessed by considering a 20% increase from baseline in serum levels of the biomarkers BDNF, GDNF and PDGF","definition_or_measurement_approach":"Biomarker serum levels (BDNF, GDNF, PDGF); effectiveness defined as ≥20% increase from baseline."}

Italy

Earliest CTIS Part Ii Submission Date

09-01-2025

Latest Decision Or Authorization Date

14-02-2025

Processing Time Days

36

Number Of Sites

4

Number Of Participants

54

Primary sponsor

Full Name

University Of Trieste

Organisation Type

Educational Institution

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Consorzio Per Valutazioni Biologiche E Farmacologiche","duties_or_roles":"sponsorDuties codes: 1,10,11,12,5,6,8","organisation_type":"Pharmaceutical company"}