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

• Register: ClinicalTrials.gov
• Last refreshed on: 15 January 2024
• Main ID: NCT03854019
• Date of registration: 22/02/2019
• Prospective Registration: Yes
• Primary sponsor: The University of Texas Health Science Center, Houston
• Public title: Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease
• Scientific title: Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease
• Date of first enrolment: August 5, 2019
• Target sample size: 20
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03854019
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Erin L Furr Stimming, MD
• Affiliation: The University of Texas Health Science Center, Houston

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Huntington Disease

Irritability

Intervention(s)

Drug: Placebo

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

Primary Outcome(s)

Irritability as Assessed by The Irritability Scale [Time Frame: 4 weeks]

Irritability as Assessed by The Irritability Scale. [Time Frame: Baseline]

Secondary Outcome(s)

Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior. [Time Frame: 4 Weeks]

Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior. [Time Frame: Baseline]

Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation [Time Frame: 4 weeks]

Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC). [Time Frame: 4 weeks]

Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC). [Time Frame: Baseline]

Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). [Time Frame: Baseline]

Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS. [Time Frame: 4 weeks]

Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS. [Time Frame: Baseline]

Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I). [Time Frame: 4 weeks]

Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS). [Time Frame: Baseline]

Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score. [Time Frame: Baseline]

Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress. [Time Frame: 4 weeks]

Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s). - Irritability/Aggression Subscale [Time Frame: Baseline]

Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s) - Irritability/Aggression Subscale [Time Frame: 4 weeks]

Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S). [Time Frame: 4 weeks]

Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS). [Time Frame: 4 weeks]

Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress. [Time Frame: Baseline]

Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain. [Time Frame: Baseline]

Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA). [Time Frame: 4 weeks]

Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC). [Time Frame: 4 weeks]

Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC). [Time Frame: Baseline]

Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation. [Time Frame: Baseline]

Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score. [Time Frame: 4 weeks]

Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA). [Time Frame: Baseline]

Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain. [Time Frame: 4 weeks]

Secondary ID(s)

HSC-MS-18-1049

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Cures Within Reach

Results

• Results available: Yes
• Date Posted: 05/01/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03854019