Inclusion Body Myositis
Conditions
Keywords
myositis, IBM, inclusion body myositis
Brief summary
Inclusion body myositis (IBM) is the most common progressive and debilitating muscle disease beginning in persons over 50 years of age. This study will assess the safety and tolerability of Arimoclomol in IBM as compared to placebo over 4 months of treatment.
Detailed description
IBM is a chronic disorder in which muscles become inflamed (swollen) and cause muscle weakening. The cause is unknown. There is new evidence to suggest that the pathology in IBM results from cellular changes induced by a variety of stressful events and diseases. In response to these stressful events the body's normal response is to increase the levels of Heat Shock Proteins (HSP) to help counteract and stop these cellular changes. In people with IBM this increase does not appear sufficient enough to reverse these toxic cellular changes. Arimoclomol causes the body to make more of this HSP protein. By increasing HSP levels in IBM patients we hope to reverse the toxic cellular changes that might be responsible for the pathology of IBM.
Interventions
DRUGArimoclomol
Arimoclomol 100 mg TID for 4 months
OTHERPlacebo
Placebo for 4 months
Sponsors
Richard Barohn, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meet the diagnostic criteria for definite or probable IBM (Griggs 1995) * Muscle function adequate for quantitative muscle testing * Age \> 50 years * Women must be postmenopausal or status post hysterectomy * For any patient currently taking medication for IBM, they must remain on current dosage for the extent of the study and last dosage change must be \> 30 days previous to enrollment
Exclusion criteria
* Presence of any one of the following medical conditions: diabetes mellitus or patients taking anti-diabetic medications, chronic infection, chronic renal insufficiency, cancer other than skin cancer less than 5 years previously, multiple sclerosis or prior episode or central nervous system demyelination, or other chronic serious medical illnesses * Presence of any of the following on routine blood screening: WBC \< 3000, platelets \< 100,000, hematocrit \< 30%, BUN \> 30 mg%, creatine \> 1.5 mg%, symptomatic liver disease with serum albumin \< 3 g/dl, PT or PTT \> upper range of control values * Women who are pregnant or lactating * History of non-compliance with other therapies * Coexistence of other neuromuscular disease * Drug or alcohol abuse within the last 3 months * Inability to give informed consent * Known bleeding disorder * Use of potentially renal toxic drugs * Prior difficulties with local anesthetic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Adverse Events Reported | Month 12 | Measure reflects the total number of adverse events reported during course of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heat Shock Protein 70 (HSP70) Levels in the Tissue | Change from Baseline to Month 4 | Biopsy taken from participants at baseline and month 4 visits. Measured change in HSP70 levels in the tissue. |
| Muscle Strength Testing | Change from Baseline to Month 4 | Change in MMT score for the period. The MMT score range is 0-5. A score of 0 is the lowest and represents no visible or palpable contraction. A score of 5 is the highest and represents full range of motion against gravity, maximal resistance. |
| Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | Change from Baseline to Month 4 | Measured change for the period. The questionnaire has 10 questions. The maximum score is 40. The higher the score the better the functional status of the patient. |
| Maximum Isometric Voluntary Contraction Testing (MVICT) Score | Change from Baseline to Month 4 | Measured MVICT using the Quantitative Muscle Assessment (QMA) system designed by Computer Source, Atlanta, GA. The system uses an adjustable cuff to attach the patient's arm or leg to an inelastic strap that is connected to force transducer with a load of 0.5 to 1,000 Newtons. Maximum force is recorded. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arimoclomol Arimoclomol 100 mg TID for 4 months | 16 |
| Placebo Matched placebo pills, 100 mg TID for 4 months | 8 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Arimoclomol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.85 years STANDARD_DEVIATION 7.86 | 68.83 years STANDARD_DEVIATION 6.7 | 66.84 years STANDARD_DEVIATION 7.49 |
| Gender Female | 4 Participants | 3 Participants | 7 Participants |
| Gender Male | 12 Participants | 5 Participants | 17 Participants |
| Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | 27.5 units on a scale STANDARD_DEVIATION 7 | 24.6 units on a scale STANDARD_DEVIATION 5.1 | 26.6 units on a scale STANDARD_DEVIATION 6.4 |
| Manual Muscle Testing (MMT) Score | 4.2 units on a scale STANDARD_DEVIATION 0.5 | 3.6 units on a scale STANDARD_DEVIATION 1.5 | 4.2 units on a scale STANDARD_DEVIATION 0.4 |
| Maximum Isometric Voluntary Contraction Testing (MVICT) Score | 130.4 newtons STANDARD_DEVIATION 70.4 | 94.4 newtons STANDARD_DEVIATION 39.8 | 119.4 newtons STANDARD_DEVIATION 63.4 |
| Region of Enrollment United Kingdom | 8 participants | 4 participants | 12 participants |
| Region of Enrollment United States | 8 participants | 4 participants | 12 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 16 | 8 / 8 |
| serious Total, serious adverse events | 0 / 16 | 1 / 8 |
Outcome results
Primary
Count of Adverse Events Reported
Measure reflects the total number of adverse events reported during course of the study.
Time frame: Month 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arimoclomol | Count of Adverse Events Reported | 109 adverse events reported |
| Placebo | Count of Adverse Events Reported | 52 adverse events reported |
Secondary
Heat Shock Protein 70 (HSP70) Levels in the Tissue
Biopsy taken from participants at baseline and month 4 visits. Measured change in HSP70 levels in the tissue.
Time frame: Change from Baseline to Month 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Heat Shock Protein 70 (HSP70) Levels in the Tissue | -110.72 ng/100ng myosin | Standard Deviation 757.4 |
| Placebo | Heat Shock Protein 70 (HSP70) Levels in the Tissue | -34.70 ng/100ng myosin | Standard Deviation 336.35 |
Secondary
Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score
Measured change for the period. The questionnaire has 10 questions. The maximum score is 40. The higher the score the better the functional status of the patient.
Time frame: Change from Baseline to Month 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | -0.34 units on a scale | Standard Deviation 1.38 |
| Placebo | Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | -0.88 units on a scale | Standard Deviation 1.16 |
Secondary
Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score
Measured change for the period. The questionnaire has 10 questions. The maximum score is 40. The higher the score the better the functional status of the patient.
Time frame: Change from Baseline to Month 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | -0.68 units on a scale | Standard Deviation 1.58 |
| Placebo | Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | -2.50 units on a scale | Standard Deviation 3.31 |
Secondary
Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score
Measured change for the period. The questionnaire has 10 questions. The maximum score is 40. The higher the score the better the functional status of the patient.
Time frame: Change from Baseline to Month 12
Population: One of the subjects that dropped from the study in the Arimoclomol arm, returned for the 12 month visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | -2.03 units on a scale | Standard Deviation 2.68 |
| Placebo | Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | -3.50 units on a scale | Standard Deviation 3.35 |
Secondary
Maximum Isometric Voluntary Contraction Testing (MVICT) Score
Measured MVICT using the Quantitative Muscle Assessment (QMA) system designed by Computer Source, Atlanta, GA. The system uses an adjustable cuff to attach the patient's arm or leg to an inelastic strap that is connected to force transducer with a load of 0.5 to 1,000 Newtons. Maximum force is recorded.
Time frame: Change from Baseline to Month 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Maximum Isometric Voluntary Contraction Testing (MVICT) Score | 7.20 newtons | Standard Deviation 19.65 |
| Placebo | Maximum Isometric Voluntary Contraction Testing (MVICT) Score | -1.71 newtons | Standard Deviation 17.8 |
Secondary
Maximum Isometric Voluntary Contraction Testing (MVICT) Score
Measured MVICT using the Quantitative Muscle Assessment (QMA) system designed by Computer Source, Atlanta, GA. The system uses an adjustable cuff to attach the patient's arm or leg to an inelastic strap that is connected to force transducer with a load of 0.5 to 1,000 Newtons. Maximum force is recorded.
Time frame: Change from Baseline to Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Maximum Isometric Voluntary Contraction Testing (MVICT) Score | -1.21 newtons | Standard Deviation 20.76 |
| Placebo | Maximum Isometric Voluntary Contraction Testing (MVICT) Score | 0.52 newtons | Standard Deviation 17.98 |
Secondary
Maximum Isometric Voluntary Contraction Testing (MVICT) Score
Measured MVICT using the Quantitative Muscle Assessment (QMA) system designed by Computer Source, Atlanta, GA. The system uses an adjustable cuff to attach the patient's arm or leg to an inelastic strap that is connected to force transducer with a load of 0.5 to 1,000 Newtons. Maximum force is recorded.
Time frame: Change from Baseline to Month 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Maximum Isometric Voluntary Contraction Testing (MVICT) Score | 0.46 newtons | Standard Deviation 12.11 |
| Placebo | Maximum Isometric Voluntary Contraction Testing (MVICT) Score | -0.30 newtons | Standard Deviation 14.49 |
Secondary
Muscle Strength Testing
Change in MMT score for the period. The MMT score range is 0-5. A score of 0 is the lowest and represents no visible or palpable contraction. A score of 5 is the highest and represents full range of motion against gravity, maximal resistance.
Time frame: Change from Baseline to Month 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Muscle Strength Testing | -0.04 units on a scale | Standard Deviation 0.19 |
| Placebo | Muscle Strength Testing | -0.12 units on a scale | Standard Deviation 0.2 |
Secondary
Muscle Strength Testing
Change in MMT score for the period. The MMT score range is 0-5. A score of 0 is the lowest and represents no visible or palpable contraction. A score of 5 is the highest and represents full range of motion against gravity, maximal resistance.
Time frame: Change from Baseline to Month 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Muscle Strength Testing | -0.12 units on a scale | Standard Deviation 0.22 |
| Placebo | Muscle Strength Testing | -0.26 units on a scale | Standard Deviation 0.27 |
Secondary
Muscle Strength Testing
Change in MMT score for the period. The MMT score range is 0-5. A score of 0 is the lowest and represents no visible or palpable contraction. A score of 5 is the highest and represents full range of motion against gravity, maximal resistance.
Time frame: Change from Baseline to Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arimoclomol | Muscle Strength Testing | -0.21 units on a scale | Standard Deviation 0.21 |
| Placebo | Muscle Strength Testing | -0.35 units on a scale | Standard Deviation 0.2 |