RecruitingPhase 1NCT04789915

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

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


Sponsor

Bjorn H. Ebdrup

Enrollment

46 participants

Start Date

May 26, 2021

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 45 Years

Inclusion Criteria1

  • Patients:

Exclusion Criteria29

  • 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
  • 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.
  • 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
  • Pregnancy (assessed by urine HCG)
  • Female patients: Unwillingness to use safe contraception (Intra Uterine Device/System or hormonal contraceptives) during the study period.
  • Severe physical illness
  • Allergies to any of the ingredients in the aripiprazole tablets or memantine tablets
  • Healthy controls:
  • Lifetime substance abuse/dependence ICD-10 (F1x.1/F1x.2) (exception: tobacco/nicotine, F17.1/F17.2)
  • Lifetime treatment with antidepressants
  • Head injury with more than 5 minutes of unconsciousness
  • Metal implanted by operation
  • Head or neck tattoos
  • Pacemaker
  • Pregnancy (assessed by urine HCG)
  • Severe physical illness

Interventions

DRUGMemantine

Add on treatment with memantine to aripiprazole.

DRUGPlacebo

Placebo add on to aripiprazole


Locations(1)

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

Glostrup Municipality, Capitol Region, Denmark

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NCT04789915


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