AMEND - Add-on MEmaNtine to Dopamine modulation to improve negative symptoms at first psychosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstadens Psykiatriske

Participant type

Patients, Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

11 Nov 2024 → 8 Apr 2025

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Lundbeckfonden

External identifiers

EU CT number

2024-513878-21-02

EudraCT number

2021-001061-20

ClinicalTrials.gov

NCT04789915

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Antipsychotics affects the brain's dopamine system, and the drugs reduce delusions, hallucinations, and disorganized thinking, which are cardinal symptoms of psychotic disorders. However, negative symptoms e.g. anhedonia, avolition, and social withdrawal, as well as cognitive deficits, are not sufficiently treated.
Memantine is used to treat Alzheimer's disease and affects the brain's glutamate system. AMEND is a 12-week, double-blind, placebo controlled, randomized clinical trial (RCT) testing effects of add-on
memantine to initial antipsychotic treatment in patients with first episode psychosis.
The main aim is to reduce negative symptoms.

Secondary objectives 1

1. Secondary outcomes are cognition, psychotic symptoms, side effects. Glutamate levels in the brain will be measured before and after 12 weeks using an ultra-high field strength (7 Tesla) magnetic resonance scanner

Conditions and MedDRA coding

First episode psychosis; ICD-10: F20.x; F22.x; F23.x; F24.x; F25.x; F28; F29

Regulatory references

Plan to share IPD

No

IPD plan description

x

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Antipsychotic-free (as defined under Exclusion Criteria below), first episode psychosis
2. Fulfilling the diagnostic criteria of schizophrenia, persistent delusional disorder, acute and transient psychotic disorders, schizoaffective disorder, other non-organic psychotic disorders and unspecified non-organic disorders (ICD-10: F20.x; F22.x; F23.x; F24.x; F25.x; F28; F29); verified by PSE interview.
3. Age: 18-45 years
4. Legally competent (In Danish: ‘myndige og habile i retslig forstand’)

Exclusion criteria 15

1. Prior use of antipsychotic medication longer than an episode of two weeks in the previous year and/or 6 weeks lifetime, and/or antipsychotic treatment within 30 days prior to inclusion.
2. Treatment with antidepressant medication the last 7 days
3. Current substance dependence ICD-10 (F1x.2) or substance abuse in any period up to 3 months prior to referral (exception: tobacco/nicotine, F17.2)
4. Head injury with more than 5 minutes of unconsciousness, lifetime
5. Any coercive measure
6. Metal implanted by operation
7. Tattoos/permanent makeup drawn before the year of 2000 or outside of approved tattoo studio (EU standards)
8. Tattoos placed within 48 hours
9. Excessive tattoos /whole body parts tattoos (assessed upon inclusion)
10. Pacemaker
11. Pregnancy (assessed by urine HCG)
12. Female patients: Unwillingness to use safe contraception (Intra Uterine Device/System or hormonal contraceptives) during the study period.
13. Severe physical illness
14. Allergies to any of the ingredients in the aripiprazole tablets or memantine tablets
15. Refusing to receive information about incidental findings on MRI

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary Endpoints Primary endpoint will be reduction in negative symptoms as measured with Positive and Negative Syndrome Scale (PANSS) negative symptoms after 12 weeks of treatment [PANSS negative baseline - PANSS negative at week 12]. Assessments will be supplemented by Brief Negative Symptom Scale (BNSS) scores.

Secondary endpoints 5

1. changes in cognition (in particular working memory, set-shifting, and attention)
2. Change in PANSS positive and PANSS total
3. clinical measures, level of functioning, side effects
4. glutamate levels in five a priori selected regions: thalamus, anterior cingulate cortex (ACC), hippocampus, dorsolateral prefrontal cortex (DLPFC), and basal ganglia.
5. Exploratory endpoints include associations between clinical data, quality of life, brain metabolites in other regions, e.g. ACC, and structural measures (e.g. hippocampus subfields), and basal ganglia quantification (See Table 1 for detailed assessments). Interactions between baseline brain metabolite levels and brain structure in patients and HC will also be investigated.

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstadens Psykiatriske

Sponsor organisation

Region Hovedstadens Psykiatriske

Address

Nordre Ringvej 69

City

Glostrup

Postcode

2600

Country

Denmark

Scientific contact point

Organisation

Region Hovedstadens Psykiatriske

Contact name

Bjørn Ebdrup

Public contact point

Organisation

Region Hovedstadens Psykiatriske

Contact name

Bjørn Ebdrup

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