Screening and Natural History: Primary Lateral Sclerosis and Related Disorders

• ClinicalTrials.gov Identifier: NCT00015444
• Recruitment Status: Completed
• First Posted: April 19, 2001
• Last Update Posted: December 16, 2019
• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Tracking Information

• First Submitted Date: April 18, 2001
• First Posted Date: April 19, 2001
• Last Update Posted Date: December 16, 2019
• Study Start Date: May 1, 2001
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: August 6, 2015): The primary outcome of this protocol is to document the natural history of clinical progression in PLS, defined as the change in clinical measures of movement speed over time: finger tapping, timed gait, and time to read a standard passage.
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Screening and Natural History: Primary Lateral Sclerosis and Related Disorders
• Official Title: Screening and Natural History: Primary Lateral Sclerosis and Related Disorders

Brief Summary

Objective:

The objectives of this protocol are:

to develop and maintain a repository of clinically characterized patients with primary lateral sclerosis for future research protocols,

to characterize the natural history of neurodegenerative disorders with corticospinal neuron degeneration,

to investigate proposed etiologies, risk factors, and biomarkers for the development of these disorders and for disease progression

Study Population:

240 patients with adult-onset progressive spasticity with a diagnosis of primary lateral sclerosis or related upper motor neuron disorder

Design:

Patients who have been referred by physicians for primary lateral sclerosis will undergo a screening evaluation at the first visit. The screening visit will include review of outside medical records, neurological examination, and diagnostic testing to determine possible causes of spasticity. Patients fulfilling the clinical criteria for primary lateral sclerosis by history or examination will be followed to determine the natural history of this disorder. Measures of motor and cognitive function will be made at baseline and follow-up visits to follow clinical progression. Magnetic resonance imaging will be carried out to determine if imaging changes occur over time. Patients identified in this protocol who are eligible for other research protocols will be invited to participate in additional protocols.

Outcome Measures:

Clinical progression will be documented by measures of finger-tapping, timed gait, speech. The association between clinical progression and MRI measures will be assessed as a secondary outcome....

Detailed Description

Objective:

The objectives of this protocol are:

• to develop and maintain a repository of clinically characterized patients with primary lateral sclerosis for future research protocols,
• to characterize the natural history of neurodegenerative disorders with corticospinal neuron degeneration,
• to investigate proposed etiologies, risk factors, and biomarkers for the development of these disorders and for disease progression

Study Population:

240 patients with adult-onset progressive spasticity with a diagnosis of primary lateral sclerosis or related upper motor neuron disorder

Design:

Patients who have been referred by physicians for primary lateral sclerosis will undergo a screening evaluation at the first visit. The screening visit will include review of outside medical records, neurological examination, and diagnostic testing to determine possible causes of spasticity. Patients fulfilling the clinical criteria for primary lateral sclerosis by history or examination will be followed to determine the natural history of this disorder. Measures of motor and cognitive function will be made at baseline and follow-up visits to follow clinical progression. Magnetic resonance imaging will be carried out to determine if imaging changes occur over time. Blood samples may be collected for measurement of potential etiologies of PLS, including risk factor genes. Patients identified in this protocol who are eligible for other research protocols will be invited to participate in additional protocols.

Outcome Measures:

Clinical progression will be documented by measures of finger-tapping, timed gait, speech. The association between clinical progression and MRI measures will be assessed as a secondary outcome.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Other
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Not Provided
• Study Population: Not Provided
• Condition: Primary Lateral Sclerosis
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

Publications *

• Leclerc KM, Landry FJ. Benign nocturnal leg cramps. Current controversies over use of quinine. Postgrad Med. 1996 Feb;99(2):177-8, 181-4.
• Bentley S. Exercise-induced muscle cramp. Proposed mechanisms and management. Sports Med. 1996 Jun;21(6):409-20. doi: 10.2165/00007256-199621060-00003.
• Auger RG. AAEM minimonograph #44: diseases associated with excess motor unit activity. Muscle Nerve. 1994 Nov;17(11):1250-63. doi: 10.1002/mus.880171103.
• Clark MG, Smallwood Shoukry R, Huang CJ, Danielian LE, Bageac D, Floeter MK. Loss of functional connectivity is an early imaging marker in primary lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2018 Nov;19(7-8):562-569. doi: 10.1080/21678421.2018.1517180. Epub 2018 Oct 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 8, 2016): 189
• Original Enrollment (submitted: June 23, 2005): 60
• Study Completion Date: April 24, 2019
• Primary Completion Date: Not Provided

Eligibility Criteria

• INCLUSION CRITERIA:
• Age 18 years of age or older
• Adult onset of progressive spasticity
• No family history of a similar disorder
• Able to provide consent or with a legally-authorized representative who can provide consent

EXCLUSION CRITERIA:

• History of stroke, cerebral palsy, traumatic brain injury or other known etiology of spasticity
• Non-neurological disorders producing muscle stiffness, such as fasciitis or rheumatological conditions
• Disorders in which pain limits the ability to move muscles, such as fibromyalgia or complex regional pain syndromes
• Profound weakness of voluntary movement
• Inability to travel to NIH
• Anticoagulation will be an exclusion for needle EMG studies
• Implanted devices or metal fragments in the brain or spinal cord will be an exclusion for MRI scanning

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00015444
• Other Study ID Numbers: 010145; 01-N-0145
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mary Kay Floeter, M.D.; National Institute of Neurological Disorders and Stroke (NINDS)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: April 24, 2019