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

• ClinicalTrials.gov Identifier: NCT04687566
• Recruitment Status: Recruiting
• First Posted: December 29, 2020
• Last Update Posted: December 29, 2020
• Sponsor: National Cheng-Kung University Hospital
• Collaborator: Ministry of Science and Technology, Taiwan
• Information provided by (Responsible Party): National Cheng-Kung University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Amphetamine Addiction; Pharmacotherapy	Drug: Dextromethorphan; Drug: Memantine; Drug: Dextromethorphan and memantine; Drug: Placebo	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment Efficacy in Dextromethorphan, Memantine Monotherapy, or Combined Use of Dextromethorphan and Memantine in Patients With Amphetamine-type Stimulants Use Disorder
• Actual Study Start Date: August 11, 2020
• Estimated Primary Completion Date: July 31, 2024
• Estimated Study Completion Date: July 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: dextromethorphan; Dextromethorphan, 60 mg per day, once daily, for 12 weeks	Drug: Dextromethorphan; The participants will take dextromethorphan 60 mg per day, once daily, for 12 weeks. The participants will be blind to the assigned treatment group.
Experimental: memantine; Memantine, 5 mg per day, once daily, for 12 weeks	Drug: Memantine; The participants will take memantine 5 mg per day, once daily, for 12 weeks. The participants will be blind to the assigned treatment group.
Experimental: dextromethorphan and memantine; Dextromethorphan (60mg per day) and memantine (5 mg per day) combination, once daily, for 12 weeks	Drug: Dextromethorphan and memantine; The participants will take dextromethorphan (60 mg per day) and memantine (5 mg per day) combination, once daily, for 12 weeks. The participants will be blind to the assigned treatment group.
Placebo Comparator: placebo; placebo, once daily, for 12 weeks	Drug: Placebo; The participants will take the placebo pills, once daily, for 12 weeks. The participants will be blind to the assigned treatment group.

Outcome Measures

Primary Outcome Measures :

1. Urinary amphetamine positive rates [ Time Frame: 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 :

1. The Wisconsin Card Sorting Test (WCST) [ Time Frame: 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.
2. The Continuous performance tests (CPT) [ Time Frame: 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.

3. The Wechsler Memory Scale - third edition (WMS-III) [ Time Frame: 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.
4. inflammatory markers [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Tzu-Yun Wang; +8862353535 ext 5940; tzuyun0105@hotmail.com

Locations

Taiwan

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; Recruiting

Tainan, Taiwan, 70428

Contact: Tzu-Yun Wang 886-6-2353535 ext 5940 tzuyun0105@hotmail.com

Sponsors and Collaborators

National Cheng-Kung University Hospital

Ministry of Science and Technology, Taiwan

Investigators

• Principal Investigator: Tzu-Yun Wang; National Cheng-Kung University Hospital

More Information

• Responsible Party: National Cheng-Kung University Hospital
• ClinicalTrials.gov Identifier: NCT04687566
• Other Study ID Numbers: MOST 109-2314-B-006-056
• First Posted: December 29, 2020
• Last Update Posted: December 29, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Cheng-Kung University Hospital:

amphetamine-type stimulants use disorder, dextromethorphan, memantine, inflammation, neurodegeneration, functional magnetic resonance imaging

Additional relevant MeSH terms:

Amphetamine-Related Disorders; Behavior, Addictive; Compulsive Behavior; Impulsive Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Memantine; Dextromethorphan; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antitussive Agents; Respiratory System Agents