Spinal and Bulbar Muscular Atrophy (SBMA)NCT02124057
Study of Hepatic Function in Patients With Spinal and Bulbar Muscular Atrophy
An observational study of Spinal and Bulbar Muscular Atrophy (SBMA) and Motor Neuron Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Spinal and bulbar muscular atrophy (SBMA) is an inherited disease. It causes weakness in muscles used for swallowing, breathing, and speaking. SBMA mainly affects men, but women can carry the gene for it. Researchers think there may be a link between SBMA and excess fat in the liver. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Spinal and Bulbar Muscular Atrophy (SBMA), Motor Neuron Disease
- How many people
- 71 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Aug 2014to 19 Nov 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: We plan to enroll men with genetically confirmed SBMA, age-matched healthy control men, SBMA carrier women, age-matched healthy control women and males with other motor neuron disease patients as disease controls.
Who may be able to join
- The study population will consist of several subgroups of patients. An individual must meet one of the following subgroup inclusion criteria to participate in this study.
- SBMA subgroup:
- Male
- Genetically confirmed SBMA
- Able to travel to the NIH
- Greater than 18 years old
Show all 32Show fewer
- SBMA carriers:
- Female
- Genetically confirmed SBMA heterozygote
- Able to travel to the NIH
- Greater than 18 years old
- Other motor neuron disease patients:
- Diagnosis of motor neuron disease other than SBMA (e.g.. amyotrophic lateral sclerosis (ALS), spinal muscular atrophy)
- Able to travel to the NIH
- Greater than 18 years old
- . Male
- Healthy male control:
- Male
- No history or diagnosis of liver disease
- No history of SBMA or other motor neuron disease
- Greater than 18 years old
- No diagnosis of diabetes or insulin resistance
- No history of alcohol abuse within the last 1 year
- No history of hyperlipidemia (LDL < 195) or hypertriglyceridemia (TAG < 225)
- Healthy female control:
- Female
- No history or diagnosis of liver disease
- No history of SBMA or other motor neuron disease
- Greater than 18 years old
- No diagnosis of diabetes or insulin resistance
- No history of alcohol abuse within the last 1 year
- No history of hyperlipidemia (LDL < 195) or hypertriglyceridemia (TAG < 225)
Who cannot join
- Diagnosed with an acquired or inherited liver disease eg., hepatitis B, hepatitis C, HIV, autoimmune hepatitis, cholestatic liver disease, Wilson s disease, iron overload disease, alpha-1 antitrypsin deficiency, hepatocellular carcinoma, (hepatic neoplasm or metastasis, etc.) or injury except for fatty liver disease.
- Contraindications to MRI such as a contraindicated non-removable metal device (i.e. pacemaker, defibrillator, insulin pump, metal clips, non-removable jewelry) or claustrophobia.
- Currently pregnant or pregnant within the past 6 months. Pregnant women are excluded from the study because of the known associated abnormalities in liver function that can occur in this population. The long term effects of MRI on the developing fetus are unknown and would present a risk with participation.
- In addition to the above criteria, the patients receiving a liver biopsy will need to meet the additional exclusion criteria below:
- Coagulopathy (PT/PTT values that are prolonged >= 3 seconds from the upper limit of normal, including treatment with oral and parenteral anticoagulants), thrombocytopenia (< 70,000), abnormal bleeding time or platelet dysfunction.
- Taking anti-platelet agents for cardiovascular protection that cannot be safely stopped for the performance of the liver biopsy.
- Obesity, which is defined as a BMI>30 at the screenig visit.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Evaluation of Hepatic Function in Patients With Spinal and Bulbar Muscular Atrophy
Background:
- Spinal and bulbar muscular atrophy (SBMA) is an inherited disease. It causes weakness in muscles used for swallowing, breathing, and speaking. SBMA mainly affects men, but women can carry the gene for it. Researchers think there may be a link between SBMA and excess fat in the liver.
Read more
Objective:
- To look for fatty liver and liver injury in people with SBMA, people with motor neuron disease, and people who carry the gene for SBMA.
Eligibility:
- Adults 18 years and older who have SBMA, have motor neuron disease, or are carriers of SBMA.
- Healthy adult volunteers.
Design:
- Participants will be screened with medical history, physical exam, and blood tests.
- Participants will have 1 outpatient visit of 1-2 days. Women will have a urine pregnancy test. All participants will have:
- Blood tests.
- Liver ultrasound. A probe is placed on the abdomen at certain locations and angles and takes pictures. The painless procedure takes 20-30 minutes.
- Liver magnetic resonance imaging (MRI) scan. The MRI scanner is a metal cylinder with a magnetic field. Participants will lie on a table that slides in and out of it. They will be in the scanner for about 30 minutes. They will get earplugs for loud noises.
- Some participants with abnormal liver testing will have a biopsy (small piece) of the liver taken. The biopsy site will be located with ultrasound, then cleaned and numbed. The physician will quickly pass a needle in and out of the liver while the participants holds their breath. Afterward, participants will be monitored in bed for 6 hours.
- Participants may return for follow-up and another 1-2 day outpatient visit yearly for up to 2 years.
Read the detailed description
Objectives:
Spinal and bulbar muscular atrophy (SBMA), or Kennedy s disease, is a slowly progressive hereditary motor neuron disease for which there is currently no effective treatment. Whether the liver is affected in SBMA is unclear. Preliminary analysis in SBMA patients has shown changes including increased hepatic fat, which requires additional investigation. Female carriers and patients with motor neuron disease will also participate in the study to evaluate for liver fat and function via imaging and laboratory tests.
Study Population:
We plan to enroll 15 men with genetically confirmed SBMA, 15 age-matched healthy control men, 15 SBMA carrier women, 15 age-matched healthy control women and 15 males with other motor neuron disease patients as disease controls. As of September 2017, recruitment is complete for men with genetically confirmed SBMA (n=15 recruited), age-matched healthy control men (n=15 recruited), SBMA carrier women (n=14 recruited), and 15 age-matched healthy control women (n=14 recruited). Recruitment of motor neuron disease subjects as disease controls for the study began in April 2018 and is ongoing. Our goal is to recruit 12 more disease control subjects.
Design:
Subjects will complete liver evaluations at the NIH that may include blood work, liver MRI imaging with spectroscopy (MRS), ultrasound, and biopsy. Liver biopsy will be performed on a subset of subjects with SBMA only, who have a clinical indication for biopsy analysis. Liver tissue will be analyzed by the NIH Clinical Center Pathology Department, and additional studies will be done in the research laboratory at NIH. Patients may undergo repeated non-invasive testing to determine if the liver findings are changing over time. An evaluation of muscle fat by MRI spectroscopy will be done with a subset of up to 10 subjects receiving the liver studies.
Outcome measures:
Subjects will be assessed using several different types of measurements including blood work for fatty metabolism, muscle function, and hepatic function. Liver biopsies will be used to determine the pattern and degree of fatty infiltration in SBMA patients. Liver and muscle imaging will be used to detect fat. Ultrasound elastography will be used to assess the extent of fibrosis and loss of elasticity in the liver.
- Keywords
- Liver, Motor Neuron Disease, Natural History
- Medical subject headings
- Bulbo-Spinal Atrophy, X-Linked, Motor Neuron Disease
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 |
|---|---|---|
| Healthy female control | Age-matched healthy control women | |
| Healthy male control | Age-matched healthy control men | |
| Other Motor Neuron Disease Patients | Male participants with other motor neuron disease | |
| SBMA Patients | Men with genetically confirmed SBMA | |
| SMBA | SBMA carrier women |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver fat deposition measured by liver MRS proton density fat fraction at the site of the dome of the liver
The primary outcome measures will be the liver fat deposition measured by liver MRS proton density fat fraction at the site of the dome of the liver. These measures will help us evaluate the prevalence and severity of fatty liver infiltration in SBMA patients compared to healthy controls.
Measured: Initial Visit and annual follow- up visits
Secondary outcomes (1)
Assessment of liver injury by biochemical analysis and thephysiological measures
The secondary outcome will be assessment of liver injury by biochemical analysis and the physiological measures (BMI, Free Testosterone, Total Testosterone). These outcome measures will help to evaluate whether the evaluated subjects have impairment of liver function by blood testing and other measurements. In addition, we hope to gain a better understanding of the relationship between testosterone levels and liver fat deposition.
Measured: Initial Visit and annual follow-up visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2014 (estimated)
- Study start4 Aug 2014
- Primary completion19 Nov 2020
- Study completion19 Nov 2020
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 Spinal and Bulbar Muscular Atrophy (SBMA)Studies 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
- 71 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christopher Grunseich, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02124057
- Sponsor's protocol ID
- 140099
- Other IDs
- 14-N-0099
- Status last verified
- Aug 2022
- First submitted
- 25 Apr 2014
- Last updated
- 18 Aug 2022
- Results posted
- No
Publications
Johnson B, Kokkinis A, Gai N, Shamim EA, Blackstone C, Fischbeck KH, Grunseich C. Nonalcoholic Fatty Liver Disease in Patients with Inherited and Sporadic Motor Neuron Degeneration. Genes (Basel). 2022 May 24;13(6):936. doi: 10.3390/genes13060936.
PubMed 35741698
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Hepatic Function in Patients With Spinal and Bulbar Muscular Atrophy
- ClinicalTrials.gov ID
- NCT02124057
- Acronym / sponsor ID
- 140099
- Keywords
- Liver, Motor Neuron Disease, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 4 Aug 2014 (actual)
- Primary completion
- 19 Nov 2020 (actual)
- Study completion
- 19 Nov 2020 (actual)
- First posted
- 28 Apr 2014 (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:
- Spinal and bulbar muscular atrophy (SBMA) is an inherited disease. It causes weakness in muscles used for swallowing, breathing, and speaking. SBMA mainly affects men, but women can carry the gene for it. Researchers think there may be a link between SBMA and excess fat in the liver.
Objective:
- To look for fatty liver and liver injury in people with SBMA, people with motor neuron disease, and people who carry the gene for SBMA.
Eligibility:
- Adults 18 years and older who have SBMA, have motor neuron disease, or are carriers of SBMA.
- Healthy adult volunteers.
Design:
- Participants will be screened with medical history, physical exam, and blood tests.
- Participants will have 1 outpatient visit of 1-2 days. Women will have a urine pregnancy test. All participants will have:
- Blood tests.
- Liver ultrasound. A probe is placed on the abdomen at certain locations and angles and takes pictures. The painless procedure takes 20-30 minutes.
- Liver magnetic resonance imaging (MRI) scan. The MRI scanner is a metal cylinder with a magnetic field. Participants will lie on a table that slides in and out of it. They will be in the scanner for about 30 minutes. They will get earplugs for loud noises.
- Some participants with abnormal liver testing will have a biopsy (small piece) of the liver taken. The biopsy site will be located with ultrasound, then cleaned and numbed. The physician will quickly pass a needle in and out of the liver while the participants holds their breath. Afterward, participants will be monitored in bed for 6 hours.
- Participants may return for follow-up and another 1-2 day outpatient visit yearly for up to 2 years.
Detailed description
Objectives:
Spinal and bulbar muscular atrophy (SBMA), or Kennedy s disease, is a slowly progressive hereditary motor neuron disease for which there is currently no effective treatment. Whether the liver is affected in SBMA is unclear. Preliminary analysis in SBMA patients has shown changes including increased hepatic fat, which requires additional investigation. Female carriers and patients with motor neuron disease will also participate in the study to evaluate for liver fat and function via imaging and laboratory tests.
Study Population:
We plan to enroll 15 men with genetically confirmed SBMA, 15 age-matched healthy control men, 15 SBMA carrier women, 15 age-matched healthy control women and 15 males with other motor neuron disease patients as disease controls. As of September 2017, recruitment is complete for men with genetically confirmed SBMA (n=15 recruited), age-matched healthy control men (n=15 recruited), SBMA carrier women (n=14 recruited), and 15 age-matched healthy control women (n=14 recruited). Recruitment of motor neuron disease subjects as disease controls for the study began in April 2018 and is ongoing. Our goal is to recruit 12 more disease control subjects.
Design:
Subjects will complete liver evaluations at the NIH that may include blood work, liver MRI imaging with spectroscopy (MRS), ultrasound, and biopsy. Liver biopsy will be performed on a subset of subjects with SBMA only, who have a clinical indication for biopsy analysis. Liver tissue will be analyzed by the NIH Clinical Center Pathology Department, and additional studies will be done in the research laboratory at NIH. Patients may undergo repeated non-invasive testing to determine if the liver findings are changing over time. An evaluation of muscle fat by MRI spectroscopy will be done with a subset of up to 10 subjects receiving the liver studies.
Outcome measures:
Subjects will be assessed using several different types of measurements including blood work for fatty metabolism, muscle function, and hepatic function. Liver biopsies will be used to determine the pattern and degree of fatty infiltration in SBMA patients. Liver and muscle imaging will be used to detect fat. Ultrasound elastography will be used to assess the extent of fibrosis and loss of elasticity in the liver.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Healthy female control | – | –Age-matched healthy control women |
| Healthy male control | – | –Age-matched healthy control men |
| Other Motor Neuron Disease Patients | – | –Male participants with other motor neuron disease |
| SBMA Patients | – | –Men with genetically confirmed SBMA |
| SMBA | – | –SBMA carrier women |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- We plan to enroll men with genetically confirmed SBMA, age-matched healthy control men, SBMA carrier women, age-matched healthy control women and males with other motor neuron disease patients as disease controls.
Key inclusion criteria (32 listed)
- The study population will consist of several subgroups of patients. An individual must meet one of the following subgroup inclusion criteria to participate in this study.
- Male
- Genetically confirmed SBMA
- Able to travel to the NIH
- Greater than 18 years old
Key exclusion criteria (7 listed)
- Diagnosed with an acquired or inherited liver disease eg., hepatitis B, hepatitis C, HIV, autoimmune hepatitis, cholestatic liver disease, Wilson s disease, iron overload disease, alpha-1 antitrypsin deficiency, hepatocellular carcinoma, (hepatic neoplasm or metastasis, etc.) or injury except for fatty liver disease.
- Contraindications to MRI such as a contraindicated non-removable metal device (i.e. pacemaker, defibrillator, insulin pump, metal clips, non-removable jewelry) or claustrophobia.
- Currently pregnant or pregnant within the past 6 months. Pregnant women are excluded from the study because of the known associated abnormalities in liver function that can occur in this population. The long term effects of MRI on the developing fetus are unknown and would present a risk with participation.
- In addition to the above criteria, the patients receiving a liver biopsy will need to meet the additional exclusion criteria below:
- Coagulopathy (PT/PTT values that are prolonged >= 3 seconds from the upper limit of normal, including treatment with oral and parenteral anticoagulants), thrombocytopenia (< 70,000), abnormal bleeding time or platelet dysfunction.
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
Liver fat deposition measured by liver MRS proton density fat fraction at the site of the dome of the liver
Time frame: Initial Visit and annual follow- up visits
The primary outcome measures will be the liver fat deposition measured by liver MRS proton density fat fraction at the site of the dome of the liver. These measures will help us evaluate the prevalence and severity of fatty liver infiltration in SBMA patients compared to healthy controls.
1 secondary outcome
Assessment of liver injury by biochemical analysis and thephysiological measures
Time frame: Initial Visit and annual follow-up visits
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2022.
- Derived from this study: PubMed 35741698Johnson B, Kokkinis A, Gai N, Shamim EA, Blackstone C, Fischbeck KH, Grunseich C. Nonalcoholic Fatty Liver Disease in Patients with Inherited and Sporadic Motor Neuron Degeneration. Genes (Basel). 2022 May 24;13(6):936. doi: 10.3390/genes13060936.
- 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.
Christopher Grunseich, 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 Spinal and Bulbar Muscular Atrophy (SBMA) and Motor Neuron Disease, 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 32 inclusion and 7 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: finished, as of the sponsor's last update on 18 Aug 2022. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Liver fat deposition measured by liver MRS proton density fat fraction at the site of the dome of the liver (time frame: Initial Visit and annual follow- up visits). 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 NCT02124057, 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 18 Aug 2022.