Dextromethorphan, Memantine Monotherapy, or Combined Use of Dextromethorphan and Memantine in Amphetamine Addiction

Phase 2

• Conditions: Pharmacotherapy; Amphetamine Addiction
• Interventions: Drug: Placebo; Drug: Dextromethorphan and memantine; Drug: Dextromethorphan; Drug: Memantine

• Registration Number: NCT04687566
• Lead Sponsor: National Cheng-Kung University Hospital

Brief Summary

The investigators will conducted a randomized double-blind placebo-controlled study to investigate the treatment outcomes of add-on low dose dextromethorphan (DM), memantine (MM), or dextromethorphan and memantine combination (DM+MM) in amphetamine-type stimulants use disorder patients.

Detailed Description

The investigators will conducted a randomized double-blind placebo-controlled study to investigate the treatment outcomes of add-on low dose dextromethorphan (60mg/day, DM), memantine (5 mg/day, MM), or dextromethorphan (60mg/day) and memantine (5mg/day) combination (DM+MM) in amphetamine-type stimulants use disorder patients. The investigators will recruit 120 patients with ATSUD in three years and allocate participants to add-on DM, MM, DM+MM or placebo group in a 1:1:1:1 ratio (participants will also undergo usual psychosocial interventions).The investigators will follow up the participants for 12 weeks and measure the treatment responses, urine drug tests, craving scales and side effects to evaluate the therapeutic effects of add-on DM, MM, or DM+MM. Neuropsychological assessments, tests for inflammatory parameters and neurotrophic factors, and brain functional magnetic resonance imaging (fMRI) will also be evaluated during 12-weeks follow up.

Study Timeline

• Study Start: 2020-08-11
• Status Verified: 2020-12
• Study First Submitted: 2020-12-14
• Study First Submitted QC: 2020-12-27
• Last Update Submitted: 2020-12-27
• Study First Posted: 2020-12-29
• Last Update Posted: 2020-12-29
• Primary Completion: 2024-07-31
• Study Completion: 2024-07-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Signed informed consent by patient or legal representative.
2. Male or female patient aged ≧20 and ≦65 years.
3. A diagnosis of ATSUD according to DSM criteria made by a specialist in psychiatry.
4. Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.

Exclusion Criteria

The presence of any of the following will exclude a patient from study enrollment:

1. Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study.
2. Females who are pregnant or lactation.
3. Other major Axis-I DSM-IV diagnosis other than ATSUD, except for tobacco use disorder, ATS induced mood or psychotic disorders.
4. Current evidence of an uncontrolled and/or clinically significant medical condition, e.g., cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation.
5. History of allergy or intolerable side effects of DM or MM.
6. Suicidal attempts or risks during screen or study period.
7. Presence of active infectious or autoimmune disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	placebo, once daily, for 12 weeks
dextromethorphan and memantine	Dextromethorphan and memantine	Dextromethorphan (60mg per day) and memantine (5 mg per day) combination, once daily, for 12 weeks
dextromethorphan	Dextromethorphan	Dextromethorphan, 60 mg per day, once daily, for 12 weeks
memantine	Memantine	Memantine, 5 mg per day, once daily, for 12 weeks

Primary Outcome Measures

Name	Time	Method
Urinary amphetamine positive rates	12 weeks	The urinary amphetamine tests will be examined during the 12 weeks of treatment period in patients with ATSUD and the results will be compared between the experimental and placebo groups.

Secondary Outcome Measures

Name	Time	Method
inflammatory markers	12 weeks	The plasma levels of cytokines and neurotrophic factors, tumor necrosis factor α (TNF-α\[pg/mL\]), C-reactive protein(CRP\[pg/mL\]), transforming growth factor β1 (TGF-β1 \[pg/mL\]), interleukin 6( IL-6\[pg/mL\]), interleukin 8(IL-8\[pg/mL\]), interleukin 1β (IL-1β\[pg/mL\]), and brain-derived neurotrophic factor(BDNF\[pg/mL\]), will be measured in patients with ATSUD at the initial screen period, day 1(baseline), week 4, 8, and 12(endpoint). We will compare the changes from screen period to the endpoint between the experimental and placebo group.
The Continuous performance tests (CPT)	12 weeks	Recognition Delayed (ARDM, range from 55-145), General Memory (GM, range from 40-168), and Working Memory (WM, range from 45-156 ). Higher scores indicate better performance.; The Continuous performance tests (CPT) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. The CPT produces a standard set of performance measures that include the number of errors of omission and errors of commission. (1) Errors of omission occur when the participant fails to respond to the target stimulus. The omission errors t-scores are ranged from 20-80 (0-100%). Higher scores indicated worse performance. (2) Errors of commission occur when the participant responds to a non-target (X) stimulus. The commission errors t-scores are ranged from 20-80 (0-100%). Higher scores indicated worse performance.
The Wechsler Memory Scale - third edition (WMS-III)	12 weeks	The Wechsler Memory Scale - third edition (WMS-III) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. WMS-III composite scores were calculated for the eight standardized primary indices: Auditory Immediate (AIM, range from 50-156), Visual Immediate (VIM, range from 47-162 ), Immediate Memory (IM, range from 40-164 ), Auditory Delayed (ADM, range from 46-162), Visual Delayed (VDM, range from 43-156), Auditory Recognition Delayed (ARDM, range from 55-145), General Memory (GM, range from 40-168), and Working Memory (WM, range from 45-156 ). Higher scores indicate better performance.
The Wisconsin Card Sorting Test (WCST)	12 weeks	The Wisconsin Card Sorting Test (WCST) will be measured in patients with ATSUD at the initial screen period and at the endpoint (after 12 weeks of treatment). We will compare the changes from screen period to the endpoint between experimental and placebo group. Performance on the WCST was scored in terms of the total number of errors (TNE, range form 0-128), perseverative errors (PE, range from 0-118), conceptual level responses (CLRs, range from 0-100%), number of categories completed (NCC, range form 0-12), and trials to complete the first category (TCC, range from 0-128). Higher scores indicate worse performance in TNE, PE, and TCC. Higher scores indicate better performance in CLRs and NCC.

Trial Locations

Locations (1)

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; 🇨🇳 Tainan, Taiwan