Double-blind, randomized, monocentric study to evaluate the efficacy and safety of memantine in adolescents with Bipolar Disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale Pediatrico Bambino Gesu

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

9 Jun 2023 → 24 Mar 2025

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministero della Salute

External identifiers

EU CT number

2024-516713-21-00

EudraCT number

2019-002778-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare the effect of memantine versus placebo in improving manic symptoms in adolescents meeting standard diagnostic criteria for BD

Secondary objectives 1

1. To compare the effect of memantine versus placebo as a mood-stabilizing agent for adolescents with BD.

Conditions and MedDRA coding

Bipolar Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. either sex, aged 13-17 years at baseline
2. DSM-5 diagnosis of BD (Type I, Type II, Cyclothymic Disorder, Unspecified) with mild to moderate symptom-severity, with current manic, mixed, or hypomanic symptoms (not psychotic) based on expert clinical assessment confirmed with structured diagnostic assessment (with Kiddie-Schedule for Affective Disorders and Schizophrenia for Schoolaged Children, Present and Lifetime version [K-SADS-PL])
3. YMRS total score of 20-40 at baseline
4. CGI-BP severity score of 4-6 at baseline
5. providing assent to participate and signed consent by a parent or legal representative
6. girls deemed to be of reproductive potential, must have a confirmed negative urine pregnancy test at intake, and use adequate contraception throughout the study

Exclusion criteria 10

1. YMRS item 8 (delusions; hallucinations) score = 8
2. exposure to any medicine that can interfere with assessments of safety, tolerability, or efficacy of memantine or placebo, or with the conduct/interpretation of the study; specifically: antipsychotic-antimanic agents including haloperidol, risperidone, quetiapine, aripiprazole, olanzapine, ziprasidone, carbamazepine, lamotrigine, valproate, and antidepressants; ketamine or other NMDA antagonists in last the month prior to enrolment
3. significant current risk of suicide (in the opinion of the Investigator or a "yes" response to suicidal ideation questions 4 or 5 on the Columbia-Suicide Severity Rating Scale [C-SSRS]) within the last 6 months;
4. intellectual disability (IQ <70), organic mental disorder, or mental disorder due to a general medical condition or substance abuse (DSM-5 criteria);
5. comorbid DSM-5 diagnosis of Substance Abuse Disorder
6. a serious or unstable general medical illness or clinically significant abnormal vital signs or ECG abnormality
7. known hypersensitivity to the active substance or to any of the excipients
8. patient with severe renal impairment (glomerular filtration rate, GFR < 29 mL/min/1.73 m2)
9. patient with severe hepatic impairment: at least one of the following parameters >= 2 ULM (referred to the range of normality of this age group and judged clinically significant by the investigators/ specialist medical consultant and/or needing medical treatment: alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT), bilirubin)
10. patient with serious forms of cardiovascular disease (severe and moderate congenital heart disease: severe and moderate ventricular septal defect, severe and moderate atrial septal defect, Tetralogy of Fallot, complete Transposition of the Great Arteries; severe and moderate valvular stenosis and prolapses; cardiac hypertrophy,), arrhythmias (atrial fibrillation, Paroxysmal supraventricular tachycardia (PSVT), atrial flutter, WolfParkinson-White (WPW), ventricular fibrillation, ventricular tachycardia, Brugada syndrome, severe Sinus bradycardia FC<40 bp/m)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Improvement of manic symptoms by the mean change in YMRS total score from intake to week 12

Secondary endpoints 5

1. Time-to-dropout from the AAT phase (days from start of experimental treatment to the start of aripiprazole add-on treatment) in memantine vs placebo arm
2. Response of [hypo]manic or mixed episodes by week 12, assessed by evaluating the percentage of subjects given memantine vs placebo showing a response of manic or mixed episodes as reduction by <=50% of the total YMRS score after 12 weeks of treatment.
3. Pct of subs completing the52-wk study andwith remission of sx measured by the combo:-Pct of pts withCGIBP improv score<=2;-Pct of pts with a reduction of>=50% at total YMRS score and CDRS-R score;-Pct of pts with aYMRS totscore<=12,aCDRS-Rtotscore<=28and aCGI-BPseverityscore<=2;-Pct of pts needing aripiprazole in add-on to the ongoing exp tx,avg duration of add-on tx and the avg dailydose needed in memantinevsplaceboarm for the52-wk
4. Percentage of subjects showing improvement at the 52-week study as measured by the following outcomes: a. Percentage of patients completing the 52 weeks of the study in memantine versus placebo group; b. Significant superior increased C-GAS score in memantine vs placebo group.
5. Safety and tolerability parameters will be evaluated by recording all adverse events (AEs) and serious adverse events (SAEs)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale Pediatrico Bambino Gesu

Sponsor organisation

Ospedale Pediatrico Bambino Gesu

Address

Piazza Di Sant'onofrio 4

City

Rome

Postcode

00165

Country

Italy

Scientific contact point

Organisation

Ospedale Pediatrico Bambino Gesu

Contact name

Giulia Serra

Public contact point

Organisation

Ospedale Pediatrico Bambino Gesu

Contact name

Giulia Serra

Third parties 1

Locations

1 EU/EEA country · 1 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 11 files

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

Application history

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