Study of Hepatic Function in Patients With Spinal and Bulbar Muscular Atrophy

NCT02124057 | Completed

• 2 other identifiers: 14009914-N-0099
• Study Type: observational
• Target: 71
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Spinal and Bulbar Muscular Atrophy (SBMA); Motor Neuron Disease

Keywords

Liver; Motor Neuron Disease; Natural History

Outcome Measures

Primary Outcomes (1)

• 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.

  Initial Visit and annual follow- up visits

Secondary Outcomes (1)

• Assessment of liver injury by biochemical analysis and thephysiological measures

  Initial Visit and annual follow-up visits

Study Arms (5)

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

Eligibility Criteria

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

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.

You may qualify if:

• SBMA subgroup:
• Male
• Genetically confirmed SBMA
• Able to travel to the NIH
• Greater than 18 years old
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 35741698 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Bulbo-Spinal Atrophy, X-Linked; Motor Neuron Disease

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Christopher Grunseich, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2014
• First Posted: April 28, 2014
• Study Start: August 4, 2014
• Primary Completion: November 19, 2020
• Study Completion: November 19, 2020
• Last Updated: August 18, 2022

Record last verified: 2022-08

Locations

US (1)