Sinemet for Spasticity and Function in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis

Study Overview
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Brief Summary
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Motivated by the success of dopaminergic drugs in treating rigidity associated with Parkinson's disease, some neurologists have used carbidopa-levodopa (Sinemet) to attempt to improve spasticity in ALS and PLS patients. However, data on the efficacy of carbidopa/levodopa is limited. Given the limited data and potential to improve the quality of life of these patients, the effectiveness of carbidopa-levodopa in ALS and PLS patients with severe spasticity should be studied. The investigators hypothesis is that administration of carbidopa-levodopa will improve spasticity in ALS and PLS patients.

Official Title
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Sinemet in ALS and PLS

Conditions
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Amyotrophic Lateral Sclerosis, Motor Neuron Disease

Intervention / Treatment
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* Drug: carbidopa-levodopa
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ALS or PLS Age greater than 18 years Clinically significant spasticity. Exclusion Criteria: Individuals currently taking carbidopa-levodopa or with known hypersensitivity of any component of carbidopa-levodopa Narrow-angle glaucoma Current use of a non-selective monoamine oxidase inhibitor (MAOI) History of malignant melanoma or suspicious skin lesions History of depression, suicidal ideation, or psychosis History of myocardial infarction, ventricular arrhythmia, or severe cardiopulmonary disease Uncontrolled hypertension Asthma Renal disease Hepatic disease Endocrine disease History of peptic ulcer Pregnant and/or breastfeeding Current participation in another interventional study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Identified participants will be randomized to receive either placebo or carbidopa-levodopa for a period of three weeks before crossing over to the other arm of the study. The two periods will be separated by a one day washout period.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: carbidopa-levodopa<br>Each tablet of carbidopa-levodopa in this study will be equivalent to half of a standard carbidopa-levodopa 25/100mg tablet. Participants will take one tablet three times a day for the first week of the study period, increasing to two tablets three times a day for the remainder of the study period. | Drug: carbidopa-levodopa<br>* Motivated by the success of dopaminergic drugs in treating rigidity associated with Parkinson's disease, some neurologists have used carbidopa-levodopa to attempt to improve spasticity in ALS and PLS patients.<br>* Other names: Sinemet;|
| Placebo Comparator: Placebo<br>Participants will take one placebo tablet three times a day for the first week of the study period, increasing to two tablets three times a day for the remainder of the study period. | Drug: Placebo Oral Tablet<br>* Placebo will be given to maintain blinding of participants and study team.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale - Change of spasticity severity from baseline with treatment and placebo | Numerical rating scale from 0-10, where 0 is no spasticity and 10 is worst possible spasticity | Weekly from screening to end of study (six weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale - Change of pain severity from baseline with treatment and placebo | Numerical rating scale from 0-10, where 0 is no pain and 10 is worst possible pain | Weekly from screening to end of study (six weeks) | 
| Visual Analog Scale - Change of muscle spasm severity from baseline with treatment and placebo | Numerical rating scale from 0-10, where 0 is no muscle spasm and 10 is worst possible muscle spasm | Weekly from screening to end of study (six weeks) | 
| Strength | Medical Research Council scale for muscle strength which grades power on a scale of 0 to 5 in relation to the maximum expected for that muscle, 0 being no movement observed to 5 being muscle contracts normally against full resistance. | At screening, at 3 weeks (following first arm), and at 6 weeks (following second arm) | 
| Spasticity | The Ashworth scale measures severity of spasticity on a scale of 1 to 5, where 1 is normal muscle tone and 5 is a rigid limb. | At screening, at 3 weeks (following first arm), and at 6 weeks (following second arm) | 
| Upper extremity function | 9-hole peg test | At screening, at 3 weeks (following first arm), and at 6 weeks (following second arm) | 
| Lower extremity function:10-meter Walk Test | 10-meter Walk Test is a performance measure used to assess walking speed in meters per second over a short distance. | At screening, at 3 weeks (following first arm), and at 6 weeks (following second arm) | 
| Lower extremity function: Timed Up and Go (TUG) Test | The TUG test measures the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down to asses a person's mobility and lower extremity function. | At screening, at 3 weeks (following first arm), and at 6 weeks (following second arm) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, PLS, Primary Lateral Sclerosis