Hereditary Spastic ParaplegiaNCT02859428
Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
An observational study of Hereditary Spastic Paraplegia, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Hereditary Spastic Paraplegia
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Nov 2016to 16 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- Patients withor metal in the cranium (excluding dental work) or eye.
- Patients with known seizure disorder.
- Patients who are unwilling or unable to participate.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31
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.
Read more
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.
Read the 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).
- Conditions
- Hereditary Spastic Paraplegia
- Keywords
- Hereditary Spastic Paraplegia
- Medical subject headings
- Spastic Paraplegia, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with hereditary spastic paraplegia (HSP) | Patients with hereditary spastic paraplegia types 3A, 4 and 31. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spastic Paraplegia Rating Scale (SPRS)
Disease progression as measured by the SPRS and SF-36 scales.
Measured: Once a year for five years
SF-36
Disease progression as measured by the SPRS and SF-36 scales.
Measured: Once a year for five years
Secondary outcomes (4)
Cortical silent period
Cortical silent period
Measured: Once a year for five years
CMCT, resting motor thresholds, MEP amplitude and MEP latency
CMCT, resting motor thresholds, MEP amplitude and MEP latency
Measured: Once a year for five years
miRNA relative quantity.
miRNA relative quantity.
Measured: Once a year for five years
Fasting Triglycerides, total Cholesterol, HDL and LDL, Leptin, Insulin levels.
Fasting Triglycerides, total Cholesterol, HDL and LDL, Leptin, Insulin levels.
Measured: Once a year for five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2016 (estimated)
- Study start18 Nov 2016
- Primary completion16 Oct 2020
- Study completion16 Oct 2020
Why it stopped: Investigator left NIH
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Spastic ParaplegiaStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Craig D Blackstone, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02859428
- Sponsor's protocol ID
- 160158
- Other IDs
- 16-N-0158
- Status last verified
- Oct 2020
- First submitted
- 6 Aug 2016
- Last updated
- 20 Oct 2020
- Results posted
- No
Publications
Ma YM, Zhao L. Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases. Behav Neurol. 2023 Nov 23;2023:8537296. doi: 10.1155/2023/8537296. eCollection 2023.
PubMed 38058356
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Disease Natural History and Biomarkers of SPG3A, SPG4 and SPG31
- ClinicalTrials.gov ID
- NCT02859428
- Acronym / sponsor ID
- 160158
- Conditions
- Hereditary Spastic Paraplegia
- Keywords
- Hereditary Spastic Paraplegia
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Investigator left NIH
- Enrolment
- 51 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 18 Nov 2016 (actual)
- Primary completion
- 16 Oct 2020 (actual)
- Study completion
- 16 Oct 2020 (actual)
- First posted
- 9 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with hereditary spastic paraplegia (HSP) | – | –Patients with hereditary spastic paraplegia types 3A, 4 and 31. |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
4 secondary outcomes
Cortical silent period
Time frame: Once a year for five years
CMCT, resting motor thresholds, MEP amplitude and MEP latency
Time frame: Once a year for five years
miRNA relative quantity.
Time frame: Once a year for five years
Fasting Triglycerides, total Cholesterol, HDL and LDL, Leptin, Insulin levels.
Time frame: Once a year for five years
Results and safety
The study was stopped early (reason given: Investigator left NIH). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2020.
- Derived from this study: PubMed 38058356Ma YM, Zhao L. Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases. Behav Neurol. 2023 Nov 23;2023:8537296. doi: 10.1155/2023/8537296. eCollection 2023.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig D Blackstone, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Spastic Paraplegia, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Investigator left NIH). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Spastic Paraplegia Rating Scale (SPRS) (time frame: Once a year for five years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02859428, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2020; AzTrials last refreshed its copy on 8 Nov 2026.