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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT02124057
First received: April 25, 2014
Last updated: NA
Last verified: March 2014
History: No changes posted
  Purpose

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.

Condition
Liver
Motor Neuron Disease

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Evaluation of Hepatic Function in Patients With Spinal and Bulbar Muscular Atrophy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Liver fat deposition, as measured by magnetic resonance spectroscopy [ Time Frame: ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: April 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
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.

Design:

Subjects will complete liver evaluations at the NIH that may include blood work, liver MRI imaging with spectroscopy (MRS), ultrasound, and biopsy. Liver biopsies will be done on up to 20 subjects with evidence of fatty liver by MRS: up to 10 subjects with SBMA, 5 female carriers, and 5 patients with other forms of motor neuron disease. Liver biopsy will be performed on a subset of subjects 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. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

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:

  1. Male
  2. Genetically confirmed SBMA
  3. Able to travel to the NIH
  4. Greater than 18 years old

SBMA carriers:

  1. Female
  2. Genetically confirmed SBMA heterozygote
  3. Able to travel to the NIH
  4. Greater than 18 years old

Other motor neuron disease patients:

  1. Diagnosis of motor neuron disease other than SBMA (e.g.. amyotrophic lateral sclerosis (ALS), spinal muscular atrophy)
  2. Able to travel to the NIH
  3. Greater than 18 years old
  4. . Male

Healthy male control:

  1. Male
  2. No history or diagnosis of liver disease
  3. No history of SBMA or other motor neuron disease
  4. Greater than 18 years old
  5. No diagnosis of diabetes or insulin resistance
  6. No history of alcohol abuse within the last 1 year
  7. No history of hyperlipidemia (LDL < 195) or hypertriglyceridemia (TAG < 225)

Healthy female control:

  1. Female
  2. No history or diagnosis of liver disease
  3. No history of SBMA or other motor neuron disease
  4. Greater than 18 years old
  5. No diagnosis of diabetes or insulin resistance
  6. No history of alcohol abuse within the last 1 year
  7. No history of hyperlipidemia (LDL < 195) or hypertriglyceridemia (TAG < 225)

EXCLUSION CRITERIA:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02124057

Contacts
Contact: Angela Kokkinis, R.N. (301) 451-8146 akokkinis@mail.cc.nih.gov
Contact: Kenneth H Fischbeck, M.D. (301) 435-9318 kf@ninds.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Kenneth H Fischbeck, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT02124057     History of Changes
Other Study ID Numbers: 140099, 14-N-0099
Study First Received: April 25, 2014
Last Updated: April 25, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Liver
Motor Neuron Disease

Additional relevant MeSH terms:
Muscular Atrophy
Motor Neuron Disease
Atrophy
Bulbo-Spinal Atrophy, X-Linked
Muscular Disorders, Atrophic
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathological Conditions, Anatomical
Signs and Symptoms
Neurodegenerative Diseases
Neuromuscular Diseases
Muscular Atrophy, Spinal
Spinal Cord Diseases
Central Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Muscular Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on July 22, 2014