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Pilot Study of Minocycline in Huntington's Disease

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ClinicalTrials.gov Identifier: NCT00277355
Recruitment Status : Completed
First Posted : January 16, 2006
Results First Posted : April 19, 2013
Last Update Posted : April 19, 2013
Sponsor:
Collaborator:
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
Merit Cudkowicz, Huntington Study Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Huntington Disease
Interventions Drug: minocycline
Drug: Matching placebo
Enrollment 114
Recruitment Details Between April 2006 and June 2007 , 134 patients were screened and 114 subjects were randomized at 12 Huntington Study Group clinical sites.
Pre-assignment Details 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.
Arm/Group Title Minocycline 100 mg Twice Daily Matching Placebo Twice Daily
Hide Arm/Group Description Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization). Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization).
Period Title: Overall Study
Started 87 27
Completed 73 22
Not Completed 14 5
Reason Not Completed
Withdrawal by Subject             3             3
Lost to Follow-up             2             2
Adverse Event             5             0
Death             3             0
Physician Decision             1             0
Arm/Group Title Minocycline 100 mg Twice Daily Matching Placebo Twice Daily Total
Hide Arm/Group Description Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization). Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization. Total of all reporting groups
Overall Number of Baseline Participants 87 27 114
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 27 participants 114 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
85
  97.7%
25
  92.6%
110
  96.5%
>=65 years
2
   2.3%
2
   7.4%
4
   3.5%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 87 participants 27 participants 114 participants
47.1  (10.3) 47.8  (10.6) 47.3  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 87 participants 27 participants 114 participants
Female
46
  52.9%
15
  55.6%
61
  53.5%
Male
41
  47.1%
12
  44.4%
53
  46.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 87 participants 27 participants 114 participants
United States 80 25 105
Canada 7 2 9
1.Primary Outcome
Title Change From Baseline to Month 18 in the Total Functional Capacity (TFC) Scale [LOCF Imputation Method]
Hide Description 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).
Time Frame Baseline to 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Minocycline 100 mg Twice Daily Matching Placebo Twice Daily
Hide Arm/Group Description:
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization.
Overall Number of Participants Analyzed 87 27
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.55  (1.85) 1.15  (1.70)
2.Secondary Outcome
Title Change From Baseline to Month 18 in the Total Functional Capacity (TFC) Scale [Regression Based Multiple Imputation Method]
Hide Description 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.
Time Frame Baseline to 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Minocycline 100 mg Twice Daily Matching Placebo Twice Daily
Hide Arm/Group Description:
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization).
Overall Number of Participants Analyzed 87 27
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.71  (1.96) 1.15  (1.70)
Time Frame Baseline to 18 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Minocycline 100 mg Twice Daily Matching Placebo Twice Daily
Hide Arm/Group Description Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization). Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization.
All-Cause Mortality
Minocycline 100 mg Twice Daily Matching Placebo Twice Daily
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Minocycline 100 mg Twice Daily Matching Placebo Twice Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/87 (12.64%)      1/27 (3.70%)    
Cardiac disorders     
Myocardial infarction  1  2/87 (2.30%)  2 0/27 (0.00%)  0
General disorders     
Chest discomfort  1  1/87 (1.15%)  1 0/27 (0.00%)  0
Chest pain  1  1/87 (1.15%)  1 0/27 (0.00%)  0
Death  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Infections and infestations     
Localized infection  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Pneumonia  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Injury, poisoning and procedural complications     
Ankle fracture * 2  1/87 (1.15%)  1 0/27 (0.00%)  0
Metabolism and nutrition disorders     
Deyhdration  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tongue neoplasm malignant stage  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Nervous system disorders     
Cerebrovascular accident  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Psychiatric disorders     
Agitated depression  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Anxiety  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Depression  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Renal and urinary disorders     
Renal failure * 2  1/87 (1.15%)  1 0/27 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Choking  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Dyspnea  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Pneumothorax  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Pulmonary embolism  2  1/87 (1.15%)  1 0/27 (0.00%)  0
Social circumstances     
Aborted pregnancy  2  0/87 (0.00%)  0 1/27 (3.70%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedRA 9.1
2
Term from vocabulary, MedDRA (9.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Minocycline 100 mg Twice Daily Matching Placebo Twice Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   74/87 (85.06%)      23/27 (85.19%)    
Gastrointestinal disorders     
Dysphagia  1  4/87 (4.60%)  2/27 (7.41%) 
Nausea  1  7/87 (8.05%)  0/27 (0.00%) 
Diarrhea  1  7/87 (8.05%)  3/27 (11.11%) 
General disorders     
Irritability  1  5/87 (5.75%)  1/27 (3.70%) 
Infections and infestations     
Bronchitis  1  0/87 (0.00%)  2/27 (7.41%) 
Gatrointestional viral  1  2/87 (2.30%)  2/27 (7.41%) 
Influenza  1  3/87 (3.45%)  2/27 (7.41%) 
Nasophyngitis  1  5/87 (5.75%)  3/27 (11.11%) 
Tooth abscess  1  0/87 (0.00%)  2/27 (7.41%) 
Injury, poisoning and procedural complications     
Back injury  1  1/87 (1.15%)  2/27 (7.41%) 
Contusion  1  3/87 (3.45%)  2/27 (7.41%) 
Fall  1  15/87 (17.24%)  6/27 (22.22%) 
Joint sprain  1  3/87 (3.45%)  3/27 (11.11%) 
Skin laceration  1  2/87 (2.30%)  4/27 (14.81%) 
Investigations     
Weight decreased * 1  3/87 (3.45%)  2/27 (7.41%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  8/87 (9.20%)  0/27 (0.00%) 
Nervous system disorders     
Balance disorder  1  9/87 (10.34%)  2/27 (7.41%) 
Chorea  1  5/87 (5.75%)  0/27 (0.00%) 
Dizziness  1  5/87 (5.75%)  0/27 (0.00%) 
Psychiatric disorders     
Anxiety  1  7/87 (8.05%)  1/27 (3.70%) 
Depressed mood  1  6/87 (6.90%)  1/27 (3.70%) 
Depression  1  6/87 (6.90%)  4/27 (14.81%) 
Insomnia  1  8/87 (9.20%)  2/27 (7.41%) 
Libido decreased  1  0/87 (0.00%)  2/27 (7.41%) 
Obsessive thoughts  1  5/87 (5.75%)  0/27 (0.00%) 
Suicidal ideation  1  1/87 (1.15%)  3/27 (11.11%) 
Respiratory, thoracic and mediastinal disorders     
Nasal congestion  1  2/87 (2.30%)  2/27 (7.41%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (9.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merit Cudkowicz, MD, MSc
Organization: Massachusetts General Hospital
Phone: 617-726-1873
EMail: mcudkowicz@partners.org
Layout table for additonal information
Responsible Party: Merit Cudkowicz, Huntington Study Group
ClinicalTrials.gov Identifier: NCT00277355     History of Changes
Other Study ID Numbers: FD-R-002588
DOMINO
First Submitted: January 12, 2006
First Posted: January 16, 2006
Results First Submitted: March 7, 2013
Results First Posted: April 19, 2013
Last Update Posted: April 19, 2013