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

Add-on MEmaNtine to Dopamine Modulation to Improve Negative Symptoms at First Psychosis (NCT04789915) is a Phase 1 interventional studying Psychosis and Negative Symptoms With Primary Psychotic Disorder, sponsored by Bjorn H. Ebdrup. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Psychosis, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 46 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: - Patients: - Antipsychotic-free(as defined under Exclusion Criteria below), first episode psychosis - 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') Who Should NOT Join This Trial: - 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 Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Patients: * Antipsychotic-free(as defined under Exclusion Criteria below), first episode psychosis * 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') Exclusion Criteria: * 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

Treatments Being Tested

DRUG

Memantine

Add on treatment with memantine to aripiprazole.

DRUG

Placebo

Placebo add on to aripiprazole

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

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

Glostrup Municipality, Capitol Region, Denmark

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04789915), the sponsor (Bjorn H. Ebdrup), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04789915 clinical trial studying?

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… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04789915?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04789915?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04789915. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04789915. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-07 · Data from ClinicalTrials.gov.