Nuovo impiego del farmaco Mirtazapina nella cura di pazienti affette da sindrome di Rett, con disturbi tipici della patologia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Trieste

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

18 Jun 2025 → ongoing

Decision date (initial)

2025-02-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515411-21-00

WHO UTN

U1111-1314-6160

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The study aims to evaluate the efficacy of Mirtazapine (MTZ) to induce improving changes in social behaviour, orofacial/respiratory and motor/physical area.
This study will provide information on what symptoms will Mirtazapine be able to correct, depending on the age and severity of the subject.

Secondary objectives 8

1. To assess the effectiveness of MTZ in improving anxiety, depression and mood.
2. To assess the effectiveness of MTZ in improving sleep quality.
3. To assess the effectiveness of MTZ in improving hand function.
4. To assess the improvement or worsening of the subject's general clinical condition over time.
5. To assess the effectiveness of the drug in reducing the severity and number of symptoms associated with Rett syndrome.
6. To assess the effectiveness in improving lung function. This will be assessed by measuring thoracic and abdominal respiratory movements, airflow, arterial oxyhaemoglobin saturation (HbSaO2), heart frequency and posture.
7. To assess the improvement in parental/carer stress. The rating scale used will be the Parenting Stress Index (PSI-SF).
8. To assess the improvement in the levels of neurotrophic factors involved in the regulation of mood and cognition.

Conditions and MedDRA coding

Rett Syndrome (RTT)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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

Exclusion criteria 8

1. They are participating in another investigational clinical trial
2. Hypersensitivity to MTZ
3. 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
4. QTcF interval at ECG > 450 msec
5. Scheduled surgery during the study
6. Severe diabetes mellitus (hyperglycaemia with values above 250/300 mg/dL)
7. Pregnancy, breastfeeding
8. Evidence of clinically significant malnutrition with BMI (or BMI) (kg/m2) <13

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 8

1. 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%)
2. 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
3. The drug will be considered effective if the Purposeful Hand Function scale (PHF) score increases at least 2 points above the baseline score.
4. The drug will be considered effective if the Clinical Global Impression of Change scale (CGI-C) has a score decrease at least 1 point
5. The drug will be considered effective if the Rett Syndrome Severity Scale (RCSS) scores decrease at least 3%, i.e. by 2 points
6. The assessment will be performed through measurements of thoracic and abdominal respiratory movements, airflow, arterial oxyhaemoglobin saturation (HbSaO2), heart rate and posture
7. 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%
8. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Trieste

Sponsor organisation

University Of Trieste

Address

Via Edoardo Weiss 2

City

Trieste

Postcode

34128

Country

Italy

Scientific contact point

Organisation

University Of Trieste

Contact name

Enrico Tongiorgi

Public contact point

Organisation

University Of Trieste

Contact name

Enrico Tongiorgi

Third parties 1

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications