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

Launched by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) · Jun 29, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a condition called Spinal and Bulbar Muscular Atrophy (SBMA), also known as Kennedy's Disease. SBMA is a genetic disease that mainly affects men and causes progressive muscle weakness and tremors over time. The main goal of the trial is to identify measurements that can help understand how this disease changes over time, such as muscle strength, function, and the size of muscles and fat.

Men over the age of 18, both those with and without SBMA, may be eligible to participate. Those with SBMA will undergo several tests, including blood and urine tests, muscle strength assessments, and imaging studies like MRI. Participants will also wear an activity tracker for 10 days every three months to monitor their daily movements. The study will take place over two years, with men who have SBMA attending five visits, while healthy participants will have just one visit. It’s important to note that certain health conditions may exclude someone from participating, so interested individuals should check if they meet the eligibility criteria before applying.

Gender

MALE

Eligibility criteria

• * INCLUSION CRITERIA:
• • 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:
• • 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
• • 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.
• • 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 (\<70,000), or abnormal bleeding time or platelet dysfunction
• • History of a bleeding disorder
• • Use of anticoagulants