Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease
Condition: Huntington Disease; Irritability
MeSH terms: Huntington Disease
Intervention: Dextromethorphan/quinidine 20mg/10mg (DM/Q 20mg/10mg); Placebo
Intervention description: 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.; Placebo once daily for 1 week, followed by placebo twice daily for subsequent 4 weeks, and finally placebo once daily for 7days.
Intervention MeSH terms: Quinidine; Dextromethorphan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Irritability

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.