Trying mirtazapine to help symptoms of Rett syndrome
Repurposing Mirtazapine in Rett Syndrome: a Multicentric Open Label Phase II Study
This trial will try mirtazapine, an antidepressant, to see if it improves mood, sleep, breathing problems, and hand control in girls and women aged 5–40 with Rett syndrome and a confirmed MECP2 mutation.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 54 (estimated) |
| Ages | 5 Years to 40 Years |
| Sex | Female |
| Sponsor | University of Trieste Academic / other |
| Locations | 4 sites (Genova and 3 other locations) |
| Trial ID | NCT07430046 on ClinicalTrials.gov |
What this trial studies
MirtaRett is a multicenter, open‑label, single‑arm phase II trial enrolling 54 females with genetically confirmed MECP2 Rett syndrome divided into three age cohorts (5–10, 11–17, 18–40 years). All participants receive mirtazapine and are followed to document safety and possible benefits on mood, sleep, respiratory dysfunction, and motor control—particularly hand use. Secondary measures include autonomic function, behavior, caregiver burden, clinical severity, and markers related to neuronal plasticity. The rationale is that RTT is associated with reduced monoamines and that preclinical MeCP2‑mutant mouse studies and small adult reports suggested symptomatic improvements with mirtazapine; the trial is conducted at several pediatric neurology centers in Italy.
Who should consider this trial
Good fit: Female patients aged 5–39 with a clinical diagnosis of Rett syndrome and a confirmed MECP2 mutation who have frequent daytime breathing dysfunction and are medically stable on current treatments are the intended participants.
Not a fit: Patients without a confirmed MECP2 mutation, males, those who are medically unstable or pregnant, or those without significant daytime breathing dysfunction are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, mirtazapine could improve sleep, mood, breathing and hand function and reduce caregiver burden for girls and women with Rett syndrome.
How similar studies have performed: Preclinical MeCP2‑mutant mouse studies and small open‑label human reports in adults showed improvements in breathing, motor and mood symptoms, but large randomized pediatric data are lacking.
Eligibility criteria
Show full inclusion / exclusion criteria
INCLUSION CRITERIA * 1\. Female aged 5 to 39 years inclusive, at the time of signing the informed consent. * 2\. Girls of childbearing age negative to pregnancy test; * 3\. Body weight \> 10 kg. and within the expected range for RTT, based on age and height. * 4\. Diagnosis of RTT based on consensus clinical criteria (Neul, 2010) and a confirmed mutation in MECP2 gene. * 5\. Breathing dysfunction (at least one of the following): period apnoea, intermittent hyperventilation, breath holding spells, air swallowing, forced expulsion of air and /or saliva. * 6\. Ten episodes or more/day of breathing dysfunction during wakefulness in the week prior to the screening visit (parents report). 7\. 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). * 8\. 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. * 9\. Written consent signed by parent/legal guardian/representative prior to screening visit * 10\. Patient is cooperative, willing to complete the study, and capable of doing so with assistance of a caregiver. * 11\. Caregiver is able to understand the instructions and fully participate. EXCLUSION CRITERIA 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.
Where this trial is running
Genova and 3 other locations
- Unità di Neuropsichiatria Infantile, IRCCS, Istituto Giannina Gaslini, Genova — Genova, Italy (Recruiting)
- UOC di Neuropsichiatria Infantile, Policlinico Universitario "Gaetano Martino" di Messina, University of Messina. Messina — Messina, Italy (Recruiting)
- Centro Epilessia - Unità Neurologia Pediatrica, ASST Ospedale Santi Carlo Paolo - Dipartimento Scienze della Salute, Università di Milano — Milan, Italy (Recruiting)
- Unità di Pediatria, Dipartimento della Donna e dei Bambini - Policlinico S. M. alle Scotte. Siena — Siena, Italy (Recruiting)
Study contacts
- Principal investigator: Enrico Tongiorgi, PhD — University of Trieste, Trieste - Italy
- Study coordinator: Enrico Tongiorgi, PhD
- Email: tongi@units.it
- Phone: +39 348 73477322
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.