A Randomized Controlled Trial on the Efficacy and Safety of Memantine on Posttraumatic Stress Disorder

JRCT ID: jRCTs031210689

Registered date:22/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: posttraumatic stress disorder post-traumatic stress disorder PTSD
• Date of first enrollment: 27/07/2023
• Target sample size: 40
• Study type: Interventional
• Intervention(s): Memantine capsules or placebo capsules will be administered daily for 17 weeks. In principle, the final dose of memantine is fixed at 20 mg. Based on the therapeutic standards of the Alzheimer's disease, daily dose of memantine will start from 5 mg. During the following five weeks of dose adjustment period, the dose will be increased every week until the maximum 20 mg as the basic protocol design. However, as far as the dose adjustment protocol is strictly followed, stopping of the increase in the dose or decreasing the dose will be allowed. After then, capsules will be administered at a fixed dose for 12 weeks. Placebo capsule will be labeled same doses as memantine and administered abiding the same protocol.

Outcome(s)

• Primary Outcome: Amelioration of PTSD symptoms as evaluated by the CAPS-5 (Clinician-Administered PTSD Scale for DSM-5) score changes from baseline to 13 weeks after the start of the capsule administration.

Secondary Outcome

We aim to assess the following factors at 13 weeks after the start of the capsule administration.

<Regarding efficacy assessments>
1. Changes in the CAPS-5 scores from baseline to each time point,
2. Changes in PDS-5 (PTSD Diagnostic Scale for DSM-5) scores from the baseline,
3. Changes in IES-R (Impact of Event Scale-Revised) scores from the baseline,
4. Changes in ITQ (International Trauma Questionnaire) scores from the baseline,
5. Changes in PTCI (Post-traumatic Cognitions Inventory) scores from the baseline,
6. Changes in DES (Dissociative Experiences Scale) scores from the baseline,
7. Changes in BDI-II (Beck Depression Inventory-II) scores from the baseline,
8. Changes in SASS-J (Social Adaptation Self-evaluation Scale Japanese edition) scores from the baseline,
9. Changes in STAI (State-Trait Anxiety Inventory) scores from the baseline,
10. Changes in CGI (Clinical Global Impression) scores from the baseline,
11. Changes in RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) scores from the baseline.

<Regarding safety assessments>
Adverse events measuring by the UKU (Udvalg for Kliniske Undersogelser, Scandinavian Society for Psychopharmacology) Side Effects Rating Scale, blood tests, blood pressure measurement from baseline to 17 weeks (If any adverse events observed, the patients will be followed after 17 weeks as possible).

<Other assessments>
1. Association between Childhood Trauma Questionnaire (CTQ) scores and changes in the primary and secondary endpoint scores,
2. Changes in inflammation related indices in the blood before and after the intervention,
3. Final administered dose of each patient.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 60age old
• Gender: Both

Include criteria

1)Patients diagnosed with a posttraumatic stress disorder (PTSD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria,
2)Patients whose age are >=18 and <=60 (18-60 years old),
3)Patients attending the National Center of Neurology and Psychiatry Hospital, collaborative institutes, or a psychiatric department in other institutes,
4)Individuals who could understand the nature of this study and provide informed consent,
5)Patients whose PDS-5 scores are >=28 at the eligibility screening point.

Exclude criteria

1)Patients with the duration of PTSD <6 months,
2)Patients whose PDS-5 scores that were acquired in the second screening changed by >=30% when compared with the scores that were acquired in the 30-day period prior to the first screening,
3)Patients who do not fulfill the criteria in terms of the adjuvant remedy and therapy defined in the study protocol,
4)Patients with drug or substance dependence,
5)Individuals who are currently undertaking or have taken three months of specific psychotherapy (e.g., prolonged exposure therapy, cognitive behavioral therapy, or eye movement desensitization and reprocessing therapy),
6)Patients with comorbidities such as schizophrenia, bipolar in severe manic state, or a status of intellectual disability or developmental disorder that can cause difficulties for participating in this study,
7)Patients with a strong or uncontrollable suicidal ideation,
8)Patients whose average daily caffeine intake are >=400 mg,
9)Patients with alcohol use disorder or alcohol withdrawal symptoms,
10)Patients with comorbid severe physical diseases (e.g., chronic pain) or injury (e.g., fracture),
11)Pregnant women,
12)Nursing mother,
13)Patients whose native language is not Japanese,
14)Individuals who cannot cooperatively adhere to the treatment contract or the study protocol,
15)Individuals who meet the Grade 3 or upper limit values of the criteria for decreasing capsule dosage, except body weight (dizziness, fall, headache, constipation, edema, anorexia, nausea, vomiting, anxiety, agitation, restlessness, blood pressure, blood glucose, CPK, creatinine, ALT, AST) at the pre-assessment,
16)Individuals with severe diseases or physical injury in the past three months, which could modulate memantine effects or make participation in the study difficult,
17)Patients with the anamnesis of epilepsy, seizure, or convulsions, or a factor which elevates urinary pH,
18)The lead research doctor or collaborative research doctors will determine those who are not eligible for this trial.

Related Information

• Primary Sponsor: Hori Hiroaki
• Source(s) of Monetary Support: National Center of Neurology and Psychiatry,The Japan Society for the Promotion of Science