Clinical, Molecular and Imaging Biomarkers in Spinal and Bulbar Muscular Atrophy (SBMA)

NCT04944940 | Recruiting

• 2 other identifiers: 10000428000428-N
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Background: SBMA is an inherited chronic disease. It affects males in mid to late adulthood. It causes slowly progressive weakness of muscles and hand tremors. Researchers want to learn more about the effects of SBMA. Objective: To identify measurements that change over time in SBMA, including tests of muscle strength and function, as well as measurements of muscle and fat size. Eligibility: Men over the age of 18 both with and without a history of SBMA. Design: Participants will have a medical history, physical exam, and blood and urine tests. They will have neuromuscular ultrasound. They will have a lumbar puncture to obtain spinal fluid. For this, a needle will be inserted into the spinal canal in the lower back. Participants will have muscle strength and function tests. These tests may include pushing, pulling, rising from a chair and sitting back down, and/or walking. During these tests, they may wear an accelerometer (activity tracker) on their wrist. Participants will get an activity tracker to wear on their wrist for 10 days at home every 3 months. Participants with SBMA will also have lower limb magnetic resonance imaging (MRI) and optional whole-body MRI. They will have lung function tests. They will have speech and swallow tests. They will complete questionnaires. They may have optional body scans to measure bone density and lean body mass. They may have optional muscle biopsies. For biopsies, a needle will be used to take a small piece of muscle from the leg. Participants with SBMA will have 5 study visits over 2 years (every 6 months). Participants without SBMA will have 1 study visit.

Conditions

Spinal and Bulbar Muscular Atrophy; Kennedys Disease; Motor Neuron Disease

Keywords

Motor Neuron Disease; Spinal and Bulbar Muscular Atrophy; Kennedys disease; Androgen Receptor; Natural History Study; Natural History

Outcome Measures

Primary Outcomes (1)

• Disease progression as measured by clinical and molecular tests

  Clinical measurements include MRI, DEXA, physical function, swallow, and pulmonary testing. Molecular measurements include serum and plasma biomarkers, muscle analysis, and urine testing.

  Baseline to visits every 6 months to 2 years

Study Arms (2)

Healthy Volunteers

Healthy male participants who are age and sex matched to the SBMA participants

Patients with Spinal and bulbar muscular atrophy (SBMA)

Male participants with genetically confirmed SBMA

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary Clinical with a confirmatory genetic testing result that is consistent with a diagnosis of spinal and bulbar muscular atrophy.

You may qualify if:

• Some restrictions are placed on participation in the study because we aim to identify disease biomarkers specific to those with early to intermediate stages of disease who would be potential candidates for future therapeutic studies.
• In order to be eligible to participate in the SBMA cohort, an individual must meet all of the following criteria:
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male, above the age of 18 years
• Genetically confirmed SBMA
• Ability of subject to understand and the willingness to sign a written informed consent document
• Ability of subject to travel to the NIH Clinical Center.
• Note: an SBMA patient who meets both of the additional following criteria will be offered an optional whole body MRI at subsequent follow-up visits:
• Spinal bulbar muscular atrophy functional rating of \< 50 (and \> 35).
• On initial whole body MRI, subject has evidence of muscle fat replacement such that the total volume of disease affected muscles (i.e., muscles with at least 10% muscle fat infiltration and no more than 50% muscle fat fraction) is at least:
• ml if only 1 muscle is eligible or
• ml if more than one muscle meets the criteria
• In order to be eligible to participate in this study in the Healthy Control cohort, an individual must meet all of the following criteria:
• Stated willingness to comply with all study procedures and availability to travel to the NIH for the duration of the study
• Male, above the age of 18 years

You may not qualify if:

• SBMA is a disease that affects males and manifests in adulthood. Thus, woman and children are not included in this study. This study will not include individuals who lack consent capacity.
• An SBMA patient who meets any of the following criteria will be excluded from participation in this study:
• Contraindications to MRI such as a contraindicated non-removable metal device (i.e., pacemaker, defibrillator, insulin pump, metal clips, non-removable jewelry) or claustrophobia.
• Non ambulatory
• Use of androgen reducing agents within the past two years
• Note: An SBMA patient who meets any of the following criteria will be excluded from the lumbar puncture procedure:
• PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
• INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
• History of a bleeding disorder
• Use of anticoagulants
• Note: An SBMA patient who meets any of the following criteria will be excluded from the muscle biopsy procedure:
• Advanced wasting of tibialis anterior that precludes needle muscle biopsy (in order to ensure that a sample taken would be of muscle and not just fat and fascia)
• Use of aspirin or non-steroidal anti-inflammatory agents 3 days prior to the procedure
• Note: An SBMA patient who meets any of the following criteria will be excluded from the whole body MRI:
• Patient has a history of prior treatment with androgen reducing agents including LHRH agonists or antagonists, androgen receptor antagonists and selective androgen receptor modifiers.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (2)

• Rhodes LE, Freeman BK, Auh S, Kokkinis AD, La Pean A, Chen C, Lehky TJ, Shrader JA, Levy EW, Harris-Love M, Di Prospero NA, Fischbeck KH. Clinical features of spinal and bulbar muscular atrophy. Brain. 2009 Dec;132(Pt 12):3242-51. doi: 10.1093/brain/awp258.

  PMID: 19846582 BACKGROUND

• Atsuta N, Watanabe H, Ito M, Banno H, Suzuki K, Katsuno M, Tanaka F, Tamakoshi A, Sobue G. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain. 2006 Jun;129(Pt 6):1446-55. doi: 10.1093/brain/awl096. Epub 2006 Apr 18.

  PMID: 16621916 BACKGROUND

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

Central Study Contacts

Angela D Kokkinis, R.N.

CONTACT

(301) 451-8146; akokkinis@mail.cc.nih.gov

Christopher Grunseich, M.D.

CONTACT

(301) 402-5423; grunseichc@mail.nih.gov

Study Design

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

Study Record Dates

• First Submitted: June 29, 2021
• First Posted: June 30, 2021
• Study Start: October 25, 2021
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)