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

NCT03929068 | Completed Phase 1 FDA Drug

• 1 other identifier: Sinemet-001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Keywords

ALS; PLS; Primary Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Visual Analog Scale - Change of pain severity from baseline with treatment and placebo

  Weekly from screening to end of study (six weeks)

• Visual Analog Scale - Change of muscle spasm severity from baseline with treatment and placebo

  Weekly from screening to end of study (six weeks)

• Strength

  At screening, at 3 weeks (following first arm), and at 6 weeks (following second arm)

• Spasticity

  At screening, at 3 weeks (following first arm), and at 6 weeks (following second arm)

• Upper extremity function

  At screening, at 3 weeks (following first arm), and at 6 weeks (following second arm)

Study Arms (2)

carbidopa-levodopa

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

carbidopa-levodopa DRUG

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.

Also known as: Sinemet

carbidopa-levodopa

Placebo Oral Tablet DRUG

Placebo will be given to maintain blinding of participants and study team.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of ALS or PLS
• Age greater than 18 years
• Clinically significant spasticity.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Timothy M Miller, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 26, 2019
• Study Start: May 13, 2019
• Primary Completion: July 8, 2022
• Study Completion: July 8, 2022
• Last Updated: July 11, 2022

Record last verified: 2022-07

Locations

US (1)