- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03854019
Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease
January 3, 2024 updated by: Erin Furr Stimming, The University of Texas Health Science Center, Houston
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Erin Furr Stimming, MD
- Phone Number: (713) 500-7033
- Email: Erin.E.Furr@uth.tmc.edu
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- The University of Texas Health Science Center at Houston
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Verified HD mutation carriers;
- Irritable as diagnosed by the Irritability Scale with a score > 14;
- Stable concomitant medication (no change of medication during last 30 days prior to inclusion);
- 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.
Exclusion Criteria:
- 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;
- Use of certain medicines to treat psychiatric disorders--chlorpromazine, haloperidol, perphenazine, pimozide, quetiapine, risperidone, thioridazine.
- Use of tamoxifen;
- Presence or history of seizures or diagnosed epilepsy;
- Severe cognitive disorders defined as a score < 18 on the MOCA;
- Clinically relevant abnormal findings in the ECG, the vitals, in the physical examination or laboratory values at screening that could interfere with the objectives of the study or the safety of the subject as judged by the investigator;
- Participation in another investigative drug trial within 2 months;
- Subjects who are unlikely to be compliant and attend scheduled clinic visits as required as determined by the Investigator.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg), then Placebo
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.
|
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.
Other Names:
Placebo once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
|
Placebo Comparator: Placebo, then Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg)
Placebo one capsule once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
|
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.
Other Names:
Placebo once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Irritability as Assessed by The Irritability Scale.
Time Frame: Baseline
|
The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.
|
Baseline
|
Irritability as Assessed by The Irritability Scale
Time Frame: 4 weeks
|
The Irritability Scale total score ranges from 0 to 42, with higher scores indicating greater irritability.
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).
Time Frame: Baseline
|
The HADS is a self-report, 14-item scale (7 items relate to anxiety and 7 relate to depression) used to determine the levels of anxiety and depression that a person is experiencing.
The total score ranges from 0 to 42 (21 per subscale), with higher scores signifying worse symptoms.
|
Baseline
|
Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).
Time Frame: 4 weeks
|
The HADS is a self-report, 14-item scale (7 items relate to anxiety and 7 relate to depression) used to determine the levels of anxiety and depression that a person is experiencing.
The total score ranges from 0 to 42 (21 per subscale), with higher scores signifying worse symptoms.
|
4 weeks
|
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.
Time Frame: Baseline
|
The NPI-Q is a 12-domain informant-based interview that assesses neuropsychiatric symptoms over the previous month.The total NPI-Q severity score ranges from 0 to 36, with higher scores indicate greater symptoms severity.
|
Baseline
|
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.
Time Frame: 4 weeks
|
The NPI-Q is a 12-domain informant-based interview that assesses neuropsychiatric symptoms over the previous month.The total NPI-Q severity score ranges from 0 to 36, with higher scores indicate greater symptoms severity.
|
4 weeks
|
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.
Time Frame: Baseline
|
Caregiver distress associated with the symptom is rated on an anchored 0- to 5-point scale, which total sum ranges from 0 to 60. Higher scores indicate greater caregiver distress related to patient's neuropsychiatric symptoms.
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Baseline
|
Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.
Time Frame: 4 weeks
|
Caregiver distress associated with the symptom is rated on an anchored 0- to 5-point scale, which total sum ranges from 0 to 60. Higher scores indicate greater caregiver distress related to patient's neuropsychiatric symptoms.
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4 weeks
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Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s). - Irritability/Aggression Subscale
Time Frame: Baseline
|
The PBA-s is a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease.
The PBA-s is an 11-item scale rating the frequency and severity of symptoms.
The total score for irritability/aggression subscale ranges from 0 to 32, with higher scores indicating greater behavioral symptoms severity.
|
Baseline
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Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s) - Irritability/Aggression Subscale
Time Frame: 4 weeks
|
The PBA-s is a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease.
The PBA-s is an 11-item scale rating the frequency and severity of symptoms.
The total score for irritability/aggression subscale ranges from 0 to 32, with higher scores indicating greater behavioral symptoms severity.
|
4 weeks
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Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS.
Time Frame: Baseline
|
The TMS comprises the motor section of the UHDRS, a 31-item subscale that comprehensively evaluates motor aspects of HD.
The overall 31 items are each rated from grade 0 (not affected) to grade 4 (most severely affected), resulting in a range of 0-124 points.
|
Baseline
|
Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS.
Time Frame: 4 weeks
|
The TMS comprises the motor section of the UHDRS, a 31-item subscale that comprehensively evaluates motor aspects of HD.
The overall 31 items are each rated from grade 0 (not affected) to grade 4 (most severely affected), resulting in a range of 0-124 points.
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4 weeks
|
Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC).
Time Frame: Baseline
|
The TMC comprises 7 of the 31 items in the TMS, which are related to chorea symptoms.
The total TMC score ranges from 0 to 28, with higher scores indicating greater chorea severity.
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Baseline
|
Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC).
Time Frame: 4 weeks
|
The TMC comprises 7 of the 31 items in the TMS, which are related to chorea symptoms.
The total TMC score ranges from 0 to 28, with higher scores indicating greater chorea severity.
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4 weeks
|
Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC).
Time Frame: Baseline
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The TFC lists five stages of Huntington's Disease and five levels of function in the domains of workplace, finances, domestic chores, activities of daily living and requirements for unskilled or skilled care.
The total TFC score ranges from 0 to 13, with higher scores signifying better functioning.
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Baseline
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Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC).
Time Frame: 4 weeks
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The TFC lists five stages of Huntington's Disease and five levels of function in the domains of workplace, finances, domestic chores, activities of daily living and requirements for unskilled or skilled care.
The total TFC score ranges from 0 to 13, with higher scores signifying better functioning.
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4 weeks
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Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation.
Time Frame: Baseline
|
The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses.
The first part (Items 1-5) rates an individual's degree of suicidal ideation on a 0-5 scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors".
The C-SSRS outcomes are categories and have binary responses (yes/no).
Suicidal ideation is considered when the patient responds a "yes" answer at any time during treatment to any one of the five suicidal ideation questions (Categories 1-5) on the C-SSRS.
The sum of the 5 intensity item scores create a total score (range 0 to 25) to represent the intensity rating (higher scores indicate more severe suicidal ideation).
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Baseline
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Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation
Time Frame: 4 weeks
|
The C-SSRS is a suicidal ideation and behavior rating scale with yes/no responses.
The first part (Items 1-5) rates an individual's degree of suicidal ideation on a 0-5 scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors".
The C-SSRS outcomes are categories and have binary responses (yes/no).
Suicidal ideation is considered when the patient responds a "yes" answer at any time during treatment to any one of the five suicidal ideation questions (Categories 1-5) on the C-SSRS.
The sum of the 5 intensity item scores create a total score (range 0 to 25) to represent the intensity rating (higher scores indicate more severe suicidal ideation).
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4 weeks
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Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior.
Time Frame: Baseline
|
The questions 6-10 of the C-SSRS are related to suicidal behavior, and the outcome is a simple yes/no response.
Suicidal behavior occurs if the patient answers a "yes" at any time during treatment to any one of the five suicidal behavior questions (Categories 6-10) on the C-SSRS.
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Baseline
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Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior.
Time Frame: 4 Weeks
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The questions 6-10 of the C-SSRS are related to suicidal behavior, and the outcome is a simple yes/no response.
Suicidal behavior occurs if the patient answers a "yes" at any time during treatment to any one of the five suicidal behavior questions (Categories 6-10) on the C-SSRS.
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4 Weeks
|
Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA).
Time Frame: Baseline
|
The MoCA is a rapid screening instrument for mild cognitive dysfunction.
It assesses different cognitive domains with a total possible score of 0 to 30 points; a score of 26 or above is considered normal for the general population.
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Baseline
|
Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA).
Time Frame: 4 weeks
|
The MoCA is a rapid screening instrument for mild cognitive dysfunction.
It assesses different cognitive domains with a total possible score of 0 to 30 points; a score of 26 or above is considered normal for the general population.
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4 weeks
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Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S).
Time Frame: Baseline
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The CGI is a stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication.
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Baseline
|
Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S).
Time Frame: 4 weeks
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The CGI is a stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication.
The CGI is a 3-item observer-rated scale that measures illness severity (CGI-S), global improvement or change (CGI-I) and therapeutic response.
The scale ranges from 1-7, with higher scores indicating worse outcomes.
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4 weeks
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Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I).
Time Frame: 4 weeks
|
The CGI is a stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication.
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4 weeks
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Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain.
Time Frame: Baseline
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The UHDRS - cognitive function assessment a phonetic verbal fluency test, the Symbol Digit Modalities Test, and the Stroop Interference Test.
These tests do not have a predefined score range, but higher scores indicate better cognitive performance.
|
Baseline
|
Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain.
Time Frame: 4 weeks
|
The UHDRS - cognitive function assessment a phonetic verbal fluency test, the Symbol Digit Modalities Test, and the Stroop Interference Test.
These tests do not have a predefined score range, but higher scores indicate better cognitive performance.
|
4 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Erin L Furr Stimming, MD, The University of Texas Health Science Center, Houston
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 5, 2019
Primary Completion (Actual)
November 11, 2022
Study Completion (Actual)
November 11, 2022
Study Registration Dates
First Submitted
February 22, 2019
First Submitted That Met QC Criteria
February 22, 2019
First Posted (Actual)
February 26, 2019
Study Record Updates
Last Update Posted (Actual)
January 5, 2024
Last Update Submitted That Met QC Criteria
January 3, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Genetic Diseases, Inborn
- Basal Ganglia Diseases
- Movement Disorders
- Neurodegenerative Diseases
- Dyskinesias
- Heredodegenerative Disorders, Nervous System
- Dementia
- Cognition Disorders
- Chorea
- Huntington Disease
- Physiological Effects of Drugs
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Anti-Infective Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Enzyme Inhibitors
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Membrane Transport Modulators
- Cytochrome P-450 Enzyme Inhibitors
- Voltage-Gated Sodium Channel Blockers
- Sodium Channel Blockers
- Cytochrome P-450 CYP2D6 Inhibitors
- Respiratory System Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Antitussive Agents
- Adrenergic alpha-Antagonists
- Dextromethorphan
- Quinidine
Other Study ID Numbers
- HSC-MS-18-1049
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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