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Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31

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ClinicalTrials.gov Identifier: NCT02859428
Recruitment Status : Recruiting
First Posted : August 9, 2016
Last Update Posted : July 23, 2020
Sponsor:
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 August 6, 2016
First Posted Date August 9, 2016
Last Update Posted Date July 23, 2020
Actual Study Start Date November 18, 2016
Estimated Primary Completion Date December 31, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 13, 2020)
  • Spastic Paraplegia Rating Scale (SPRS) [ Time Frame: Once a year for five years ]
    Disease progression as measured by the SPRS and SF-36 scales.
  • SF-36 [ Time Frame: Once a year for five years ]
    Disease progression as measured by the SPRS and SF-36 scales.
Original Primary Outcome Measures
 (submitted: August 6, 2016)
  • Spastic Paraplegia Rating Scale (SPRS) [ Time Frame: Ongoing ]
  • SF-36 [ Time Frame: Ongoing ]
Change History
Current Secondary Outcome Measures
 (submitted: February 13, 2020)
  • Cortical silent period [ Time Frame: Once a year for five years ]
    Cortical silent period
  • CMCT, resting motor thresholds, MEP amplitude and MEP latency [ Time Frame: Once a year for five years ]
    CMCT, resting motor thresholds, MEP amplitude and MEP latency
  • miRNA relative quantity. [ Time Frame: Once a year for five years ]
    miRNA relative quantity.
  • Fasting Triglycerides, total Cholesterol, HDL and LDL, Leptin, Insulin levels. [ Time Frame: Once a year for five years ]
    Fasting Triglycerides, total Cholesterol, HDL and LDL, Leptin, Insulin levels.
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 Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
Official Title Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31
Brief Summary

Background:

Hereditary spastic paraplegia (HSP) usually progresses slowly. Researchers want to learn more about how its symptoms change over time. They want to look for changes in the blood and cells of people with the most common forms of HSP that might allow them to better understand the disease.

Objectives:

To learn more about common forms of hereditary spastic paraplegia and find out how it progresses over time.

Eligibility:

People age 7 and older with SPG3A, SPG4A, or SPG31

Design:

Participants will have 1 two-hour visit each year for up to 5 years.

At 1 visit, adult participants may have a skin biopsy. An area of skin will be numbed then a tool will remove a small piece of skin.

At all visits, all participants will have a physical exam and blood drawn.

At all visits, participants will do a few tasks like walking quickly and climbing stairs.

Participants can give permission for their skin cells, DNA samples, and data to be used in other studies. The samples and data will have no identifying information.

Detailed Description

The Neurogenetics Branch (NGB) within the National Institute of Neurological Disorders and Stroke (NINDS) is conducting a study to evaluate patients with hereditary spastic paraplegia types 3A, 4 and 31. The objective of this study is to understand disease progression in these closely related forms of hereditary spastic paraplegia using validated rating scales such as the Spastic Paraplegia Rating Scale (SPRS), and Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36). We also hope to develop biomarkers that could be used in future treatment trials from human serum and by utilizing transcranial magnetic stimulation (TMS) to determine central motor conduction times and resting motor thresholds.

OBJECTIVES

The primary objective of this protocol is to study the natural history of the most common forms of autosomal dominant hereditary spastic paraplegia. The information obtained from validated rating scales (SPRS and SF-36), TMS, and serum biomarkers, will allow for the development of treatment trials. In some cases, blood or other biologic samples (including skin biopsies) will be obtained for future laboratory studies.

STUDY POPULATION

The number of participants to be enrolled will be set to 300.

DESIGN

This is an observational study of autosomal dominant forms of hereditary spastic paraplegia progression, pathophysiology, and biomarkers.

OUTCOME MEASURES

In this study we will track disease progression using the Spastic Paraplegia Rating Scale (SPRS) and SF-36. Also, we will measure levels of plasma lipids, insulin, leptin, and of certain micro RNAs to investigate their utility as biomarkers. We will utilize TMS (combined with nerve conducting studies) to assess central motor conduction times (CMCT) and resting motor thresholds (RMT).

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients with a diagnosis of HSP caused by mutations of known pathological significance or variants of unknown significance at the genomic loci associated with the genes ATL1, SPAST and REEP1.
Condition Hereditary Spastic Paraplegia
Intervention Not Provided
Study Groups/Cohorts Patients with hereditary spastic paraplegia (HSP)
Patients with hereditary spastic paraplegia types 3A, 4 and 31.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: August 6, 2016)
300
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2029
Estimated Primary Completion Date December 31, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • INCLUSION CRITERIA:
  • 7 years or older.
  • Proven genetic diagnosis or variant of unknown significance considered by the Principal Investigator (PI) to be likely pathogenic at genomic loci associated with SPG3A, SPG4 and SPG31.
  • For the subcomponent involving transcranial magnetic stimulation (TMS) / nerve conduction studies, patients must be greater than or equal to 18 years of age and would be willing to undergo the procedure.

EXCLUSION CRITERIA:

  • Adults unable to provide consent or minors without a parent or a guardian.
  • Unwillingness to consent for collection of biological samples or their cryopreservation.
  • Any bleeding disorder that would prevent or present any danger either during blood extraction or skin biopsy, such hemophilia, or the long-term use of anticoagulants such as Coumadin.
  • For the subcomponent of this study involving transcranial magnetic stimulation (TMS), performed with nerve conduction studies:

    • Patients under 18 years of age.
    • Patients withwith implanted devices, such as pacemakers, pumps or stimulators.
    • Patients withor metal in the cranium (excluding dental work) or eye.
    • Patients with known seizure disorder.
    • Patients who are unwilling or unable to participate.
Sex/Gender
Sexes Eligible for Study: All
Ages 7 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Elizabeth J Hartnett (301) 402-8274 elizabeth.hartnett@nih.gov
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02859428
Other Study ID Numbers 160158
16-N-0158
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
Study Sponsor National Institute of Neurological Disorders and Stroke (NINDS)
Collaborators Not Provided
Investigators
Principal Investigator: Craig D Blackstone, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date April 8, 2020