Sinemet for Spasticity and Function in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis (ALS and PLS)

Sinemet in ALS and PLS

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.

Study Overview

• Status: Completed
• Conditions: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: carbidopa-levodopa; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: carbidopa-levodopa; 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; 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.; Other Names: Sinemet
Placebo Comparator: Placebo; 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; Placebo will be given to maintain blinding of participants and study team.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Timothy M Miller, MD, PhD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Actual): July 8, 2022
• Study Completion (Actual): July 8, 2022

Study Registration Dates

• First Submitted: April 10, 2019
• First Submitted That Met QC Criteria: April 24, 2019
• First Posted (Actual): April 26, 2019

Study Record Updates

• Last Update Posted (Actual): July 11, 2022
• Last Update Submitted That Met QC Criteria: July 8, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: ALS; Primary Lateral Sclerosis; PLS
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination
• Other Study ID Numbers: Sinemet-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No