Clinical trial NCT03854019: Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease
Official title: Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Huntington Disease
Irritability
Keywords: Irritability
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Cures Within Reach
First posted: 2019-02-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Irritability as Assessed by The Irritability Scale.
timeFrame: Baseline
measure: Irritability as Assessed by The Irritability Scale
timeFrame: 4 weeks
Secondary outcomes:
measure: Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).
timeFrame: Baseline
measure: Behavioral Symptoms, as Assessed by the Hospital Anxiety and Depression Scale (HADS).
timeFrame: 4 weeks
measure: Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.
timeFrame: Baseline
measure: Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Severity Score.
timeFrame: 4 weeks
measure: Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.
timeFrame: Baseline
measure: Behavioral Symptoms, as Assessed by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) - Caregiver Distress.
timeFrame: 4 weeks
measure: Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s). - Irritability/Aggression Subscale
timeFrame: Baseline
measure: Behavioral Symptoms, as Assessed by the Problem Behaviors Assessment - Short Version (PBA-s) - Irritability/Aggression Subscale
timeFrame: 4 weeks
measure: Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS.
timeFrame: Baseline
measure: Motor Symptoms, as Assessed by the Total Motor Score (TMS) From the UHDRS.
timeFrame: 4 weeks
measure: Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC).
timeFrame: Baseline
measure: Motor Symptoms, as Assessed by the Total Maximal Chorea (TMC).
timeFrame: 4 weeks
measure: Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC).
timeFrame: Baseline
measure: Functional Independence, as Assessed by the UHDRS Total Functional Capacity Scale (TFC).
timeFrame: 4 weeks
measure: Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation.
timeFrame: Baseline
measure: Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Ideation
timeFrame: 4 weeks
measure: Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior.
timeFrame: Baseline
measure: Number of Participants With Behavioral Suicidal Events, as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) - Suicidal Behavior.
timeFrame: 4 Weeks
measure: Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA).
timeFrame: Baseline
measure: Cognitive Symptoms, as Assessed by the The Montreal Cognitive Assessment (MoCA).
timeFrame: 4 weeks
measure: Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S).
timeFrame: Baseline
measure: Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Severity Scale (CGI-S).
timeFrame: 4 weeks
measure: Patient Progress and Treatment Response Over Time, as Assessed by the Clinical Global Impressions Improvement Scale (CGI-I).
timeFrame: 4 weeks
measure: Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain.
timeFrame: Baseline
measure: Cognitive Symptoms, as Assessed by the Unified Huntington's Disease Rating Scale (UHDRS) - Cognitive Domain.
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Erin L Furr Stimming, MD
role: PRINCIPAL_INVESTIGATOR
References: