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Protocol Details

An Observational Study to Assess Clinical, Molecular and Imaging Biomarkers in Spinal and Bulbar Muscular Atrophy (SBMA)

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000428-N

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required

No

Population Exclusion(s)

Female;
Children

Keywords

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

Recruitment Keyword(s)

None

Condition(s)

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

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Neurological Disorders and Stroke

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.

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Eligibility

INCLUSION CRITERIA:

Some restrictions are placed on participation in the study because we aim to identify disease biomarkers specific to those with early t 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:

--500ml if only 1 muscle is eligible or

--250ml 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

-No history of SBMA or other neuromuscular disorder

-No history of facial palsy

-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.

EXCLUSION CRITERIA:

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

-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

-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 (less than 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.

-Patient is unable to complete the study assessments of QMT or timed walk tests.

-Patient anticipates making major lifestyle changes during the observation period relating to diet and exercise.

A Healthy Control participant who meets any of the following criteria will be excluded from the study:

-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 (less than 70,000), or abnormal bleeding time or platelet dysfunction

-History of a bleeding disorder

-Use of anticoagulants


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Citations:

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Contacts:

Principal Investigator

Referral Contact

For more information:

Christopher Grunseich, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
NIHBC 35 - PNRC I BG RM 2A-1010
35 CONVENT DR
BETHESDA MD 20892
(301) 402-5423
grunseichc@mail.nih.gov

Angela Kokkinis, R.N.
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health
Building 10
Room 5S-219
10 Center Drive
Bethesda, Maryland 20892
(301) 451-8146
akokkinis@mail.cc.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT04944940

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