Pilot Study of Minocycline in Huntington's Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: minocycline; Drug: Matching placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • University of British Columbia
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • University of Alabama at Birmingham
  • Colorado
    • Englewood, Colorado, United States
      • Colorado Neurological Institute
  • Florida
    • Gainesville, Florida, United States
      • University of Florida
    • Tampa, Florida, United States
      • University of South Florida
  • Maryland
    • Baltimore, Maryland, United States
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States
      • Massachusetts General Hospital
  • Missouri
    • St. Louis, Missouri, United States
      • Washington University School of Medicine
  • New York
    • Albany, New York, United States
      • Albany Medical College
    • New York, New York, United States
      • Columbia University
    • Rochester, New York, United States
      • University of Rochester
  • Texas
    • Galveston, Texas, United States
      • University of Texas Medical Branch at Galveston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Merit Cudkowicz
• Collaborators: FDA Office of Orphan Products Development
• Investigators: Principal Investigator: Merit E. Cudkowicz, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Huntington Study Group. Minocycline safety and tolerability in Huntington disease. Neurology. 2004 Aug 10;63(3):547-9. doi: 10.1212/01.wnl.0000133403.30559.ff.

Helpful Links

• The Huntington Study Group (HSG) is a non-profit group of physicians and other health care providers from medical centers in the U.S., Canada, Europe and Australia, experienced in the care of Huntington patients and dedicated to clinical research of HD.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: January 12, 2006
• First Submitted That Met QC Criteria: January 12, 2006
• First Posted (Estimate): January 16, 2006

Study Record Updates

• Last Update Posted (Estimate): April 19, 2013
• Last Update Submitted That Met QC Criteria: April 17, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Study of Minocycline in Huntington's Disease
• 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; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: FD-R-002588; DOMINO