Repurposing Mirtazapine in Rett Syndrome

NCT07430046 | Recruiting Phase 2 DMC

• 2 other identifiers: CTIS ID: 283662024-515411-21-00
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 4

Brief Summary

Rett Syndrome (RTT) is a rare neurodevelopmental disorder caused by an MECP2 gene mutation on the X chromosome, primarily affecting females. It causes progressive motor and cognitive decline, loss of speech, repetitive hand movements, breathing issues, seizures, and sleep problems. Given RTT's association with reduced monoamine levels, antidepressants like mirtazapine (MTZ) may help.Preclinical studies in MeCP2-mutant mice and early adult RTT trials showed that MTZ improved respiratory, motor, and neurological function, sleep, and mood, prompting this pediatric and young adult study. The MirtaRett trial is a multicenter, open-label, single-arm, phase II study enrolling 54 female RTT patients (ages 5-40), divided into groups of 18 (5-10, 11-17, 18-40 years). It aims to evaluate MTZ's safety and efficacy for mood, sleep, and motor symptoms, particularly hand control. Other ares of investigation include autonomic function, behavior, caregiver burden, clinical severity, and neuronal plasticity and metabolic biomarkers. Patients will receive escalating doses of MTZ oral solution: initial low doses (3.75-15 mg/day) for two weeks, followed by optimal doses (7.5-30 mg/day) for six months. Safety, tolerability, and symptoms will be monitored over 10 months (3-month screening, 6-month treatment, 1-month follow-up). The study is conducted at four Italian RTT-specialized hospitals, led by the University of Trieste. Partner sites are in Italy, specifically at the hospitals in Milan, Genova, Siena, and Messina.

Conditions

RETT Syndrome With Proven MECP2 Mutation

Keywords

antidepressant; mirtazapine; motor dysfunction; cognitive impairment; sleep disorder; cognitive disability; parent stress

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint: Improvement in the rating scale 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 the pre-treatment value.

  From enrollment to the end of treatment at 24 weeks

Secondary Outcomes (24)

• Secondary endpoint 1. Reduced mood and anxiety disorder symptoms

  From enrollment to the end of treatment at 24 weeks

• Secondary Endpoint 1bis: Reduced mood and anxiety disorder symptoms

  From enrollment to the end of treatment at 24 weeks

• Secondary Endpoint 2-a. Improved Vital parameters

  From enrollment to the end of treatment at 24 weeks

• Secondary Endpoint 2-b. Improved Vital parameters

  From enrollment to the end of treatment at 24 weeks

• Secondary Endpoint 2-c. Improved Vital parameters

  From enrollment to the end of treatment at 24 weeks

Study Arms (1)

Rett syndrome patients with MECP2 mutation and 5-40 years of age

EXPERIMENTAL

Subjects included in the study are female patients with a diagnosis of RTT, confirmed by mutation of the MECP2 gene, and who meet the inclusion/exclusion criteria of the study. The total number of participating patients is 54, aged between 5 and 40 years, divided into three groups of 18 patients each (5-10 years, 11-17 years and 18-40 years). The study medication mirtazapine oral solution (MTZ) will be given once daily at bedtime. During the first 14 days of the treatment period, MTZ at Dose Level 1 will be used to achieve the planned target daily dose, according to age (3.75 mg for 5-10 yrs, 7.5 mg for 11-17 yrs and 15 mg \>18 yrs, from day 1 to 14). From Day 15 to the end of week 24, Dose Level 2 will be achieved: 7.5 mg for 5-10 yrs, 15 mg for 11-17 yrs and 30 mg for \> 18 yrs).

Drug: mirtazapine

Interventions

mirtazapine DRUG

Study medication (3.75 mg, 7.5 mg, 15 mg, 30 mg of MTZ oral solution) will be given once daily at bedtime. During the first 14 days of the treatment period, the oral solution of the active drug at Dose Level 1 will be used to achieve the planned target daily dose, according to age (3.75 mg for 5-10 yrs, 7.5 mg for 11-17 yrs and 15 mg \> 18 yrs, from day 1 to 14). From Day 15 to the end of week 24, Dose Level 2 will be achieved: 7.5 mg for 5-10 yrs, 15 mg for 11-17 yrs and 30 mg for \> 18 yrs).

Also known as: MirtaPil oral solution, Remeron oral solution

Rett syndrome patients with MECP2 mutation and 5-40 years of age

Eligibility Criteria

• Age: 5 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. Female aged 5 to 39 years inclusive, at the time of signing the informed consent.
• \. Girls of childbearing age negative to pregnancy test;
• \. Body weight \> 10 kg. and within the expected range for RTT, based on age and height.
• \. Diagnosis of RTT based on consensus clinical criteria (Neul, 2010) and a confirmed mutation in MECP2 gene.
• \. Breathing dysfunction (at least one of the following): period apnoea, intermittent hyperventilation, breath holding spells, air swallowing, forced expulsion of air and /or saliva.
• \. Ten episodes or more/day of breathing dysfunction during wakefulness in the week prior to the screening visit (parents report).
• \. Stable medication regimen for 4 weeks prior to beginning the study (if receiving services - physical, occupational, or speech therapy - subjects must be on a stable regimen of these services for 3 months prior to beginning the study).
• \. Female patients of childbearing potential must use a highly effective contraceptive method such as combined hormonal contraception (containing estrogen and progestin) associated with ovulation suppression (oral, intravaginal, transdermal); progestin-only hormonal contraception associated with ovulation suppression (oral, injectable, implantable); intrauterine device; hormone-releasing intrauterine system. Sexual abstinence is considered a highly effective contraceptive method if it aligns with the individual's usual lifestyle. Female patients of childbearing potential are to use adequate contraception as recommended by their Health Care Provider.
• \. Written consent signed by parent/legal guardian/representative prior to screening visit
• \. Patient is cooperative, willing to complete the study, and capable of doing so with assistance of a caregiver.
• \. Caregiver is able to understand the instructions and fully participate.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Patient is participating to another investigational clinical trial.
• Hypersensitivity to MTZ or any of the other ingredients of Mirtapil®.
• 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.
• QTcF interval on the ECG greater than 450 msec
• Surgery planned during the study.
• Severe diabetes mellitus (hyperglycaemia with values above 250/300 mg/dL);
• Pregnancy, breastfeeding.
• Evidence of clinically significant malnutrition with BMI (or BMI) (kg/m2) \<
• Patients who manifested prior suicidal ideation.

Sponsors & Collaborators

• University of Trieste: lead
• Policlinico G . Martino, Messina Italy: collaborator
• IRCSS Gianna Gaslini, Genova, Italy: collaborator
• Policlinico S.Maria alle Scotte, Siena, Italy: collaborator
• ASST Ospedale Santi Paolo e Carlo, Milano, Italy: collaborator

Study Sites (4)

Unità di Neuropsichiatria Infantile, IRCCS, Istituto Giannina Gaslini, Genova

Genova, 16147, Italy

RECRUITING

UOC di Neuropsichiatria Infantile, Policlinico Universitario "Gaetano Martino" di Messina, University of Messina. Messina

Messina, 98125, Italy

RECRUITING

Centro Epilessia - Unità Neurologia Pediatrica, ASST Ospedale Santi Carlo Paolo - Dipartimento Scienze della Salute, Università di Milano

Milan, 20142, Italy

RECRUITING

Unità di Pediatria, Dipartimento della Donna e dei Bambini - Policlinico S. M. alle Scotte. Siena

Siena, 53100, Italy

RECRUITING

MeSH Terms

Conditions

Neurologic Manifestations; Cognitive Dysfunction; Sleep Wake Disorders

Interventions

Mirtazapine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Enrico Tongiorgi, PhD

  University of Trieste, Trieste - Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Enrico Tongiorgi, PhD

CONTACT

+39 348 73477322; tongi@units.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: February 24, 2026
• Study Start: July 9, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4)