Down Syndrome
Conditions
Keywords
catatonia
Brief summary
This study evaluates the efficacy of transcranial direct current stimulation (tDCS) for depression with catatonia in individuals with Down syndrome (DS). 62 patients will be randomized to receive 15 sessions of active or sham tDCS. The primary objective is to measure changes in depressive/catatonic symptoms using the Bush-Francis Catatonia Rating Scale (BFCRS). Secondary objectives include safety, cognitive effects, EEG correlates, and biological markers (cortisol, BDNF, cytokines). The study aims to provide a non-pharmacological therapeutic alternative for this population
Detailed description
Justification: Depression is common in individuals with Down syndrome (DS), often accompanied by catatonia, and is under-treated. Conventional treatments are limited by tolerability and linguistic difficulties. Transcranial direct current stimulation (tDCS), safe and effective, has never been tested in DS. Hypothesis: tDCS is effective and safe for depression with catatonia in DS, improving mood, cognition, and motor symptoms. Objectives: Primary: To evaluate the clinical efficacy of 15 sessions of bifrontal tDCS on depression with catatonia in DS (Bush-Francis Catatonia Rating Scale (BFCRS)). Secondary: To evaluate safety, long-term clinical and cognitive effects (1 and 3 months), EEG correlates, and biological effects (cortisol, BDNF, cytokines). Methodology: Multicenter (2 sites), randomized, double-blind, placebo-controlled study. 30 DS patients will receive 15 sessions of active tDCS (2 mA, 20 min, anode over left DLPFC, cathode over right DLPFC) or sham tDCS. Outcomes: Primary: Changes in depressive/catatonic symptoms (BFCRS) between Day 0 and Day 5. Secondary: Safety, clinical (MADRS, UPDRS), cognitive (SIB), EEG, and biological (blood, saliva) assessments. Target Population: Men and women with DS with a depressive episode and catatonia (30 patients). Inclusion Criteria: DS, age \> 18 years, major depression with catatonia (DSM-5), informed consent. Exclusion Criteria: Pregnancy, contraindication to tDCS, refusal. Statistical Analyses: ANOVA or mixed models for BFCRS scores. Justification for Inclusion: To provide a safe, non-pharmacological therapeutic alternative. Withdrawal Criteria: Withdrawal of consent, severe pathology. Procedures: Clinical, cognitive, EEG, and biological (blood, saliva) assessments at Day 0, Day 1, Day 5, 1 and 3 months. Recruitment: 6 sites (CH Vinatier Lyon, CHU Nantes, CHU Dijon, CHU Clermont Ferrand, CH Rouen, GHU Neurosciences Paris). EEG and biological analyses at Lyon and Paris only. Number of Subjects: 62 patients (31 per group). Duration: Inclusion (24 months), individual participation (3 months), total study (27 months). Locations: CH Le Vinatier (Lyon), CHU Nantes, CHU Dijon, CHU Clermont Ferrand, CH Rouen, GHU Neurosciences Paris. Benefit-Risk Ratio: Pioneering study on tDCS in DS, aiming for a safe alternative to current treatments and a better understanding of neurobiological mechanisms.
Interventions
DEVICETranscranial stimulation
A randomized, 2-arm, sham-controlled study, patients with Down syndrome presenting with major depressive episode (DSM5) with catatonic features will be randomly allocated to receive 15 sessions of either active (20 min, 2mA, ramp up/down 30 sec) or sham tDCS (20 min, ramp up/down 30 sec at the beginning and at the end of each stimulation session), thrice daily. Each stimulation session will be spaced at least two hours apart. The anode will be placed over the left DLPFC, the cathode over the right DLPFC using the Beam F3 algorithm in order to individualize target location based on head circumference, tragus to tragus and inion to nasion distances.
Sponsors
Hôpital le Vinatier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Multicenter (6 sites), randomized, double-blind, parallel-group controlled study. Patients will be randomly assigned to a group receiving 15 sessions of active tDCS (3 sessions per day for 5 days, from D0 to D5, with the tDCS anode placed over the left DLPFC and the cathode over the right DLPFC, located using the international 10/20 electrode placement system, each stimulation lasting 20 minutes at 2mA), or to a group receiving 15 sessions of sham stimulation (same electrode montage and stimulation duration, but without current). Participation in the EEG and biology component will be limited to the Lyon and Paris centers.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with Down syndrome * Age \> 18 * Diagnosis of Major Depressive Disorder MDD with catatonic symptoms according to the DSM-5 criteria * Informed consent signed by the patient, by the patient under curatorship, or by the legal representative in the case of a patient under guardianship. * Person affiliated to the French social security system or equivalent
Exclusion criteria
* Pregnancy (checked with a pregnancy test) * Contraindication for tDCS(i.e., cochlear implant) * Refusal of the patients or their legal representatives * Other persons protected under the CSP (judicial safeguard, family habilitation)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute changes on depressive / catatonic symptoms between D0 and D5 measured with the Bush-Francis Catatonia Rating Scale (BFCRS) | 27 months | The primary outcome will be the acute changes in the severity of catatonic symptoms measured by the BFCRS evaluated before treatment (D0) and after the tDCS regimen (D5). The analyses will be performed on a strict intention-to-treat sample of the evaluable patients defined in the protocol as patients with a baseline assessment and at least one post-tDCS score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in clinical and cognitive will be also assessed at M1 and M3, allowing the evaluation of tDCS-induced long-term effects | 27 months | Bush-Francis Catatonia Rating Scale (BFCRS) |
Countries
France
Contacts
CONTACTJEROME J BRUNELIN, PhD, HDR)
CONTACTVERONIQUE V VIAL
PRINCIPAL_INVESTIGATORCAROLINE C DEMILY, MD PhD HDR
HOPITAL VINATIER
Outcome results
None listed