Add-on MEmaNtine to Dopamine Modulation to Improve Negative Symptoms at First Psychosis

NCT04789915 | Recruiting Phase 1 DMC

• 1 other identifier: 2021-001061-20
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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 never-treated patients with first-episode psychosis. The main aim is to reduce negative symptoms. 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. AMEND will apply rational drug repurposing to optimize treatment of patients experiencing their first psychotic episode.

Conditions

Psychosis; Negative Symptoms With Primary Psychotic Disorder

Keywords

Memantine; Aripiprazole; 7 tesla MR

Outcome Measures

Primary Outcomes (2)

• Negative Symptom change, PANSS negative subscore

  Change in negative symptoms measured on the Positive and negative syndrome scale (PANSS), negative symptom subscore total. Scale from 7 to 49, lower values indicating better outcome.

  12 weeks

• Negative Symptom change, Brief Negative Symptom Scale (BNSS)

  Change in negative symptoms measured on the Brief Negative Symptom Scale (BNSS). Scale from 0 to 90, lower values indicating better outcome.

  12 weeks

Secondary Outcomes (9)

• PANSS total

  12 weeks

• PANSS positive

  12 weeks

• Cognition, CANTAB

  12 weeks

• Cognition, BACS

  12 weeks

• MR spectroscopy 1

  12 weeks

Other Outcomes (7)

• Quality of life, self rated by patients

  12 weeks

• MR exploratory outcomes, spectroscopy

  12 weeks

• MR exploratory outcomes, structural data 1

  12 weeks

Study Arms (2)

Memantine + aripiprazole

ACTIVE COMPARATOR

Tablet memantine or placebo will be initiated at 10mg/day for 1 week, hereafter the dose will be increased to 20mg/day until end of trial. The tablets will be identical and be provided in 10mg tablets or 20 mg tablets. (12 weeks of treatment). Tablet aripiprazole will be administered in doses starting at 5-10 mg/day. Doses will be increased slowly according to effect and side effects up to 30 mg/day.

Drug: Memantine

Placebo + aripiprazole

PLACEBO COMPARATOR

Coated placebo tablets will be provided to match memantine. Placebo equivalent of 10mg/day for 1 week, hereafter the dose will be increased to 20mg/day until end of trial. (12 weeks of treatment). Tablet aripiprazole will be administered in doses starting at 5-10 mg/day. Doses will be increased slowly according to effect and side effects up to 30 mg/day.

Drug: Placebo

Interventions

Memantine DRUG

Add on treatment with memantine to aripiprazole.

Memantine + aripiprazole

Placebo DRUG

Placebo add on to aripiprazole

Placebo + aripiprazole

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients:

You may not qualify if:

• 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.
• Age: 18-45 years
• Legally competent (In Danish: 'myndige og habile i retslig forstand')
• Healthy controls:
• No first-degree relative with known major psychiatric disorder (ICD-10: F1x; F2x; F3x)
• Age 18-45 years
• Legally competent (In Danish: 'myndige og habile i retslig forstand')
• Patients
• Treatment with antidepressant medication the last 7 days
• 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)
• Head injury with more than 5 minutes of unconsciousness, lifetime
• Any coercive measure
• Metal implanted by operation
• Head or neck tattoos
• Pacemaker

Sponsors & Collaborators

• Bjorn H. Ebdrup: lead
• Lundbeck Foundation: collaborator
• Danish Research Centre for Magnetic Resonance: collaborator

Study Sites (1)

Centre for Neuropsychiatric Schizophrenia Research, CNSR & Centre for Clinical Intervention & Neuropsychiatric Schizophrenia Research, CINS

Glostrup Municipality, Capitol Region, 2600, Denmark

RECRUITING

Related Publications (1)

• Sandstrom KO, Baltzersen OB, Marsman A, Lemvigh CK, Boer VO, Bojesen KB, Nielsen MO, Lundell H, Sulaiman DK, Sorensen ME, Fagerlund B, Lahti AC, Syeda WT, Pantelis C, Petersen ET, Glenthoj BY, Siebner HR, Ebdrup BH. Add-On MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis- the AMEND Trial Protocol. Front Psychiatry. 2022 May 20;13:889572. doi: 10.3389/fpsyt.2022.889572. eCollection 2022.

  PMID: 35669271 DERIVED

MeSH Terms

Conditions

Psychotic Disorders

Interventions

Memantine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Olga B Baltzersen, MD

  CNSR, Metal Health Centre Glostrup

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bjorn H Ebdrup, MD, PhD

CONTACT

+4538640840; bebdrup@cnsr.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD PhD, leader of CNSR

Model Details: Placebo-controlled, randomized clinical trial

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 10, 2021
• Study Start: May 26, 2021
• Primary Completion: July 1, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 9, 2024

Record last verified: 2024-12

Locations

DK (1)