Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease

NCT03854019 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: HSC-MS-18-1049
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess efficacy and safety of dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg) in patients with irritability due to Huntington's disease.

Conditions

Huntington Disease; Irritability

Keywords

Irritability

Outcome Measures

Primary Outcomes (2)

• Irritability as Assessed by The Irritability Scale.

  The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.

  Baseline

• Irritability as Assessed by The Irritability Scale

  The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.

  4 weeks

Secondary Outcomes (25)

• Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).

  Baseline

• Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).

  4 weeks

• Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.

  Baseline

• Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.

  4 weeks

• Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.

  Baseline

Study Arms (2)

Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg), then Placebo

EXPERIMENTAL

Dextromethorphan/quinidine (DM/Q) 20mg/10mg one capsule once daily for 1 week, followed by DM/Q 20mg /10 mg twice daily for subsequent 4 weeks, and finally DM/Q 20mg/10mg once daily for 7days.

Drug: Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg); Drug: Placebo

Placebo, then Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg)

PLACEBO COMPARATOR

Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.

Drug: Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg); Drug: Placebo

Interventions

Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg) DRUG

DM/Q 20mg/10mg one capsule once daily for 1 week, followed by DM/Q 20mg /10 mg twice daily for subsequent 4 weeks, and finally DM/Q 20mg/10mg once daily for 7days.

Also known as: Nuedexta

Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg), then Placebo; Placebo, then Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg)

Placebo DRUG

Placebo once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.

Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg), then Placebo; Placebo, then Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Verified HD mutation carriers;
• Irritable as diagnosed by the Irritability Scale with a score \> 14;
• Written informed consent by prospective study participant before conduct of any trial-related procedure. Participant must be able to make an informed decision of whether or not to participate in the study.

You may not qualify if:

• Hypersensitivity to dextromethorphan (e.g., rash, hives), quinine, mefloquine, quinidine, or dextromethorphan/quinidine with a history of thrombocytopenia, hepatitis, bone marrow depression or lupus-like syndrome induced by these drugs;
• Pregnant or nursing women;
• Active suicidality based on the answer "yes" in questions 4 and 5 of the Columbia-Suicide Severity Rating Scale (baseline version);
• Woman of childbearing potential, not using highly effective methods of contraception such as oral, topical or injected contraception, IUD, contraceptive vaginal ring, or double barrier method such as diaphragm and condom with spermicide) or not surgically sterile (via hysterectomy, ovarectomy or bilateral tubal ligation) or not at least one year post-menopausal;
• Male not using an acceptable barrier method for contraception;
• Presence of any medically not controllable disease (e.g. uncontrolled arterial hypertension or diabetes mellitus);
• Clinically significant renal (calculated creatinine clearance \< 30 ml/min) or hepatic dysfunction;
• Patients with pre-existing hepatic disease;
• Individuals with a history or complete heart block, QTc prolongation or tornadoes de pointes, or at high risk of complete AV block;
• Family history of congenital QT prolongation;
• History of unexplained syncope within the past year;
• Use of drugs containing quinidine, quinine, or mefloquine;
• Individuals currently taking strong CYP3A4 inhibitors or tetrabenazine;
• Use of certain antidepressants--amitriptyline, clomipramine, desipramine, fluoxetine, paroxetine, sertraline, venlafaxine;
• Use of certain heart rhythm medications--amiodarone, flecainide, procainamide, propafenone;

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• Cures Within Reach: collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Zadegan SA, Calderon O, Karagas N, Patino J, Dongarwar D, Duncan B, Teixeira AL, Rocha NP, Furr Stimming E. Assessing the efficacy of dextromethorphan/quinidine in treating irritability in Huntington's disease. J Huntingtons Dis. 2026 Jan 7:18796397251411112. doi: 10.1177/18796397251411112. Online ahead of print.

  PMID: 41499296 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

Dextromethorphan; Quinidine; dextromethorphan - quinidine combination

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cinchona Alkaloids; Quinuclidines; Quinolines; Heterocyclic Compounds, 2-Ring

Results Point of Contact

• Title: Erin Furr Stimming, MD
• Organization: The University of Texas Health Science Center at Houston

Erin.E.Furr@uth.tmc.edu

713-500-7033

Study Officials

• Erin L Furr Stimming, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: February 26, 2019
• Study Start: August 5, 2019
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: January 5, 2024
• Results First Posted: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)