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| ID | Type | Description | Link |
|---|---|---|---|
| DOMINO |
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| Name | Class |
|---|---|
| FDA Office of Orphan Products Development | FED |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Minocycline | Experimental | Minocycline (3:1 randomization) 100 mg capsules taken by mouth twice daily, 200 mg per day total for 18 months treatment duration. |
|
| Matching placebo | Placebo Comparator | Sugar pill manufactured to mimic minocycline, 1 capsule taken by mouth twice daily for 18 months treatment duration. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| minocycline | Drug | Minocycline: Oral; minocycline 100 mg capsules administered twice a day with the morning and evening meal (~ 8 hours apart) |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Merit E. Cudkowicz, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | United States | |||
| Colorado Neurological Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15304592 | Background | 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. |
| Label | URL |
|---|---|
| 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. | View source |
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20 subjects were excluded from group assignment after screening: 14 failed inclusion criteria and 6 withdrew consent. Minocycline 90 days prior to baseline and open-label during trial not permitted. Other tetracyclines, investigational drugs, lithium, digoxin, methoflurane anesthesia, theophylline and lupus-symptom causing drugs not permitted.
Between April 2006 and June 2007 , 134 patients were screened and 114 subjects were randomized at 12 Huntington Study Group clinical sites.
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| ID | Title | Description |
|---|---|---|
| FG000 | Minocycline 100 mg Twice Daily | Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization). |
| FG001 | Matching Placebo Twice Daily | Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Minocycline 100 mg Twice Daily | Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization). |
| BG001 | Matching Placebo Twice Daily | Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | The primary analyses were performed according to the intent to treat principle and included all randomized subjects. Two strategies were used to address missing data: 1. Last observation carried forward (LOCF) was used to impute missing values and 2. A secondary method of regression-based multiple imputation was also used. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 18 months |
|
Baseline to 18 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Minocycline 100 mg Twice Daily | Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial infarction | Cardiac disorders | MedRA 9.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysphagia | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merit Cudkowicz, MD, MSc | Massachusetts General Hospital | 617-726-1873 | mcudkowicz@partners.org |
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| ID | Term |
|---|---|
| D006816 | Huntington Disease |
| ID | Term |
|---|---|
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D008911 | Minocycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Matching placebo | Drug | Matching placebo 1 capsule twice daily, 18 months treatment duration. |
|
| Baseline to 18 months |
| Englewood |
| Colorado |
| United States |
| University of Florida | Gainesville | Florida | United States |
| University of South Florida | Tampa | Florida | United States |
| University of Maryland School of Medicine | Baltimore | Maryland | United States |
| Massachusetts General Hospital | Boston | Massachusetts | United States |
| Washington University School of Medicine | St Louis | Missouri | United States |
| Albany Medical College | Albany | New York | United States |
| Columbia University | New York | New York | United States |
| University of Rochester | Rochester | New York | United States |
| University of Texas Medical Branch at Galveston | Galveston | Texas | United States |
| University of British Columbia | Vancouver | British Columbia | Canada |
| Adverse Event |
|
| Death |
|
| Physician Decision |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Minocycline 100 mg Twice Daily |
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization). |
| OG001 | Matching Placebo Twice Daily | Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization. |
|
|
| Secondary | 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. | The primary analyses were performed according to the intent to treat principle and included all randomized subjects. Two strategies were used to address missing data: 1. Last observation carried forward (LOCF) was used to impute missing values and 2. A secondary method of regression-based multiple imputation was also used. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 18 months |
|
|
|
| 11 |
| 87 |
| 74 |
| 87 |
| EG001 | Matching Placebo Twice Daily | Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization. | 1 | 27 | 23 | 27 |
| Chest discomfort | General disorders | MedRA 9.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedRA 9.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA (9.1) | Systematic Assessment |
|
| Localized infection | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (9.1) | Non-systematic Assessment |
|
| Deyhdration | Metabolism and nutrition disorders | MedDRA (9.1) | Systematic Assessment |
|
| Tongue neoplasm malignant stage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (9.1) | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| Agitated depression | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA (9.1) | Non-systematic Assessment |
|
| Choking | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Aborted pregnancy | Social circumstances | MedDRA (9.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Irritability | General disorders | MedDRA (9.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Gatrointestional viral | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Nasophyngitis | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| Back injury | Injury, poisoning and procedural complications | MedDRA (9.1) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (9.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (9.1) | Systematic Assessment |
|
| Joint sprain | Injury, poisoning and procedural complications | MedDRA (9.1) | Systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (9.1) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (9.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| Chorea | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Libido decreased | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Obsessive thoughts | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | MedDRA (9.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
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| D003704 | Dementia |
| D002819 | Chorea |
| D020820 | Dyskinesias |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |