Pilot Study of Minocycline in Huntington's Disease

Study Overview
=================
Brief Summary
-----------------
This study is being conducted to assess the impact of minocycline on the progression of symptoms of HD. The study will also assess whether it is reasonable to continue with further study of minocycline in HD. We will measure the effect of minocycline on HD by measuring the change in Huntington's disease symptoms.

Detailed Description
-----------------
The DOMINO study is a randomized, double-blind, multi-center, futility study of minocycline in patients with HD. Subjects will be randomized (3:1) to one of the two study arms: (1) the group that receives active minocycline (100 mg po b.i.d.), and (2) the group that receives placebo. Subjects will be enrolled over an approximate six-month period and remain on blinded study drug for 18 months. The primary analysis will involve a comparison of the change over time in TFC between the minocycline group and a fixed value determined from historical control data. A placebo group will also be included to facilitate blinding and to permit a descriptive assessment of the validity of the assumed change over time in historical controls.

Official Title
-----------------
A Multi-Center, Double-Blind, Pilot Study of Minocycline in Huntington's Disease

Conditions
-----------------
Huntington Disease

Intervention / Treatment
-----------------
* Drug: minocycline
* Drug: Matching placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years or older Clinical features of HD and a confirmatory family history of HD; and/or genetically confirmed HD Independently walking and fully self-sufficient in activities of daily living (eating, dressing, bathing) Able to take medication (capsules) by mouth Exclusion Criteria: History of known hypersensitivity or intolerability to minocycline or known allergy to any tetracycline History of vestibular disease Subjects with underlying hematologic, hepatic or renal disease History of systemic lupus erythematosus (SLE)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline<br>Minocycline (3:1 randomization) 100 mg capsules taken by mouth twice daily, 200 mg per day total for 18 months treatment duration. | Drug: minocycline<br>* Minocycline: Oral; minocycline 100 mg capsules administered twice a day with the morning and evening meal (  8 hours apart)<br>|
| Placebo Comparator: Matching placebo<br>Sugar pill manufactured to mimic minocycline, 1 capsule taken by mouth twice daily for 18 months treatment duration. | Drug: Matching placebo<br>* Matching placebo 1 capsule twice daily, 18 months treatment duration.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Month 18 in the Total Functional Capacity (TFC) Scale [LOCF Imputation Method] | Establish preliminary estimate of minocycline's impact on progression of HD (measured by the change in Total Functional Capacity (TFC) score of Unified Huntington's Disease Rating Scale [UHDRS] between baseline & Month 18), and to assess futility of further study of minocycline. TFC consists of five ordinally scaled items assessing a person's capacity with: 1. occupation 2. financial affairs 3. domestic responsibilities 4. activities of daily living and 5. independent living. Total score ranges from zero (worst) to 13 (best). | Baseline to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Month 18 in the Total Functional Capacity (TFC) Scale [Regression Based Multiple Imputation Method] | TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best). Regression based imputation was used to impute missing values. | Baseline to 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Study of Minocycline in Huntington's Disease