Trial Outcomes & Findings for Pilot Study of Minocycline in Huntington's Disease (NCT NCT00277355)
NCT ID: NCT00277355
Last Updated: 2013-04-19
Results Overview
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).
COMPLETED
PHASE2/PHASE3
114 participants
Baseline to 18 months
2013-04-19
Participant Flow
Between April 2006 and June 2007 , 134 patients were screened and 114 subjects were randomized at 12 Huntington Study Group clinical sites.
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.
Participant milestones
| Measure |
Minocycline 100 mg Twice Daily
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
|
Matching Placebo Twice Daily
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization).
|
|---|---|---|
|
Overall Study
STARTED
|
87
|
27
|
|
Overall Study
COMPLETED
|
73
|
22
|
|
Overall Study
NOT COMPLETED
|
14
|
5
|
Reasons for withdrawal
| Measure |
Minocycline 100 mg Twice Daily
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
|
Matching Placebo Twice Daily
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization).
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
|
Overall Study
Adverse Event
|
5
|
0
|
|
Overall Study
Death
|
3
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
Pilot Study of Minocycline in Huntington's Disease
Baseline characteristics by cohort
| Measure |
Minocycline 100 mg Twice Daily
n=87 Participants
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
|
Matching Placebo Twice Daily
n=27 Participants
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization.
|
Total
n=114 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
85 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
110 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Age Continuous
|
47.1 years
STANDARD_DEVIATION 10.3 • n=99 Participants
|
47.8 years
STANDARD_DEVIATION 10.6 • n=107 Participants
|
47.3 years
STANDARD_DEVIATION 10.4 • n=206 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
61 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
53 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
80 participants
n=99 Participants
|
25 participants
n=107 Participants
|
105 participants
n=206 Participants
|
|
Region of Enrollment
Canada
|
7 participants
n=99 Participants
|
2 participants
n=107 Participants
|
9 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to 18 monthsPopulation: 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.
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).
Outcome measures
| Measure |
Minocycline 100 mg Twice Daily
n=87 Participants
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
|
Matching Placebo Twice Daily
n=27 Participants
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization.
|
|---|---|---|
|
Change From Baseline to Month 18 in the Total Functional Capacity (TFC) Scale [LOCF Imputation Method]
|
1.55 units on a scale
Standard Deviation 1.85
|
1.15 units on a scale
Standard Deviation 1.70
|
SECONDARY outcome
Timeframe: Baseline to 18 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Minocycline 100 mg Twice Daily
n=87 Participants
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
|
Matching Placebo Twice Daily
n=27 Participants
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization.
|
|---|---|---|
|
Change From Baseline to Month 18 in the Total Functional Capacity (TFC) Scale [Regression Based Multiple Imputation Method]
|
1.71 units on a scale
Standard Deviation 1.96
|
1.15 units on a scale
Standard Deviation 1.70
|
Adverse Events
Minocycline 100 mg Twice Daily
Matching Placebo Twice Daily
Serious adverse events
| Measure |
Minocycline 100 mg Twice Daily
n=87 participants at risk
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
|
Matching Placebo Twice Daily
n=27 participants at risk
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization.
|
|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
2.3%
2/87 • Number of events 2 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
General disorders
Chest discomfort
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
General disorders
Chest pain
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
General disorders
Death
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Infections and infestations
Localized infection
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Infections and infestations
Pneumonia
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Metabolism and nutrition disorders
Deyhdration
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue neoplasm malignant stage
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Nervous system disorders
Cerebrovascular accident
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Psychiatric disorders
Agitated depression
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Psychiatric disorders
Anxiety
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Psychiatric disorders
Depression
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Renal and urinary disorders
Renal failure
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.1%
1/87 • Number of events 1 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Social circumstances
Aborted pregnancy
|
0.00%
0/87 • Baseline to 18 months
|
3.7%
1/27 • Number of events 1 • Baseline to 18 months
|
Other adverse events
| Measure |
Minocycline 100 mg Twice Daily
n=87 participants at risk
Minocycline 100 mg/twice daily (minocycline to placebo 3:1 ratio randomization).
|
Matching Placebo Twice Daily
n=27 participants at risk
Matching placebo twice daily (minocycline to placebo 3:1 ratio randomization.
|
|---|---|---|
|
Gastrointestinal disorders
Dysphagia
|
4.6%
4/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Gastrointestinal disorders
Nausea
|
8.0%
7/87 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
General disorders
Irritability
|
5.7%
5/87 • Baseline to 18 months
|
3.7%
1/27 • Baseline to 18 months
|
|
Infections and infestations
Bronchitis
|
0.00%
0/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Infections and infestations
Gatrointestional viral
|
2.3%
2/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Infections and infestations
Influenza
|
3.4%
3/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Infections and infestations
Nasophyngitis
|
5.7%
5/87 • Baseline to 18 months
|
11.1%
3/27 • Baseline to 18 months
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Injury, poisoning and procedural complications
Back injury
|
1.1%
1/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Injury, poisoning and procedural complications
Contusion
|
3.4%
3/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Injury, poisoning and procedural complications
Fall
|
17.2%
15/87 • Baseline to 18 months
|
22.2%
6/27 • Baseline to 18 months
|
|
Injury, poisoning and procedural complications
Joint sprain
|
3.4%
3/87 • Baseline to 18 months
|
11.1%
3/27 • Baseline to 18 months
|
|
Injury, poisoning and procedural complications
Skin laceration
|
2.3%
2/87 • Baseline to 18 months
|
14.8%
4/27 • Baseline to 18 months
|
|
Investigations
Weight decreased
|
3.4%
3/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.2%
8/87 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Nervous system disorders
Balance disorder
|
10.3%
9/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Nervous system disorders
Chorea
|
5.7%
5/87 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Nervous system disorders
Dizziness
|
5.7%
5/87 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Psychiatric disorders
Anxiety
|
8.0%
7/87 • Baseline to 18 months
|
3.7%
1/27 • Baseline to 18 months
|
|
Psychiatric disorders
Depressed mood
|
6.9%
6/87 • Baseline to 18 months
|
3.7%
1/27 • Baseline to 18 months
|
|
Psychiatric disorders
Depression
|
6.9%
6/87 • Baseline to 18 months
|
14.8%
4/27 • Baseline to 18 months
|
|
Psychiatric disorders
Insomnia
|
9.2%
8/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Psychiatric disorders
Libido decreased
|
0.00%
0/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Psychiatric disorders
Obsessive thoughts
|
5.7%
5/87 • Baseline to 18 months
|
0.00%
0/27 • Baseline to 18 months
|
|
Psychiatric disorders
Suicidal ideation
|
1.1%
1/87 • Baseline to 18 months
|
11.1%
3/27 • Baseline to 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.3%
2/87 • Baseline to 18 months
|
7.4%
2/27 • Baseline to 18 months
|
|
Gastrointestinal disorders
Diarrhea
|
8.0%
7/87 • Baseline to 18 months
|
11.1%
3/27 • Baseline to 18 months
|
Additional Information
Merit Cudkowicz, MD, MSc
Massachusetts General Hospital
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place