Investigating Loss of Neuromuscular Junction Transmission Fidelity in Older Adults (STAMINA)

Sarcopenia is a condition characterised by age-related loss of muscle mass and function. Factors affecting the strength of muscle contraction independent of mass, such as neuromuscular junction (NMJ) transmission, are increasingly suspected as important contributors to the development of age-related physical disability. The group of investigators leading the current study, have recently demonstrated NMJ transmission deficits in aged mice, but whether this translates in older human individuals is not known

The primary aim is to assess whether clinically meaningfull muscle weakness is associated with NMJ transmission deficits in older human individuals with clinically meaningfull muscle weakness.

The secondary aim is to assess whether NMJ transmission deficits correlate with different measures of functional capacity to inform future trials of the most appropriate choice of tests.

Study Overview

• Status: Completed
• Conditions: Sarcopenia

Detailed Description

The study is a cross-sectional pilot study and will be led by investigators:

1. Professor Brian Clark, PhD, Ohio University
2. Professor William David Arnold, MD, Ohio State University

Up to 16 older (>70 yrs.) individuals and 8 healthy younger (18-50 yrs.) individuals will be included in this cross-sectional pilot study. To assess whether clinically meaningfull muscle weakness is associated with NMJ transmission failure, results from single fiber EMG analyses and repetitive nerve stimulation in older individuals with clinically meaningfull muscle weakness will be compared to those obtained in older adults without muscle weakness and with healthy young individuals. To assess whether NMJ transmission deficits correlates with different measures of functional capacity, a series of different functional tests will be performed.

• Study Type: Observational
• Enrollment (Actual): 19

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Athens, Ohio, United States, 45701
      • Ohio University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study candidates will be referred by community physicians and other local health care providers or self-referred. Local advertising will be used to raise awareness of the study. Specifically, subjects will be recruited in one of the following ways:

1. Through short presentations about the research project made in classes or at local community events.
2. Email to the university community and/or the OMNI database soliciting potential volunteers.

Description

Inclusion Criteria

• Men and women 70+ years of age OR men and women 18-50 years old
• Body mass index between 19 and 40 kg/m2.
• Willingness to undergo all testing procedures, maintain current diet during the study period, and adhere to the study protocol.

Exclusion Criteria:

• Neuromuscular Disease (ie. movement disorder, or overt neurological disease, such as Sensory Neuropathy with Sensory Ataxia, Apraxia, Post-Polio Syndrome, Mitochondrial Myopathy, Myelopathy, myasthenia gravis)
• Neurological Disease (ie. Dementia (Alzheimers, multi-infarct, fronto-temporal); multiple sclerosis, amyotrophic lateral sclerosis, Parkinsons Disease, cerebellar ataxia, or significant cognitive impairment (a score of 22 or less on the Montreal Cognitive Assessment (MOCA))
• Musculoskeletal disorders (ie. rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, acute gout or osteoarthritis limiting mobility)
• Terminal illness(i.e., Cancer, myeloma, acute leukaemia)
• Uncontrolled Psychiatric disorder (ie. bipolar, schizophrenia, major depression)
• Cardiovascular Diseases (ie. NYHA Class III or IV congestive heart failure, clinically significant aortic stenosis, recent history of cardiac arrest, uncontrolled atrial fibrillation, use of a cardiac defibrillator, or uncontrolled angina or hypertension)
• Other significant conditions (ie, that would impact safety and/or compliance to the protocol (e.g. chronic renal failure requiring peritoneal or hemodialysis, chronic liver disease, blood dyscrasia, carcinoma within last 3 years, severe inflammatory bowel disease, severe respiratory disease (uncontrolled asthma, COPD), etc)
• Drug or alcohol abuse
• Not meeting MRI eligibility (e.g. metal implants, reported pregnancy or positive pregnancy test at the time of imaging for women aged 55 years or younger);
• Not meeting the DEXA eligibility (e.g. reported pregnancy or positive pregnancy test at the time of imaging for women aged 55 years or younger);
• Failure to provide informed consent;
• Subjects who do not answer "male" or female" to the question of biological sex
• Currently or recently (within the last 1 year) taking gender affirming hormones.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Older Individuals
Healthy young to middle aged Individuals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single Fiber Electromyography (sfEMG)	sfEMG of the vastus lateralis will be performed to ascertain NMJ transmission at a minimum of 30 synapses per participant.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repetitive Nerve Stimulation	As additional measures of NMJ transmission, Repetitive Nerve Stimulation (3Hz) of the spinal accessory nerve (recorded from the trapezius) and fibular nerve (recorded from tibialis anterior) will be performed	Baseline
Magnetic Resonance Imaging	Assessment of thigh muscle cross-sectional area	Baseline
Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of appendicular lean mass	Baseline
Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of total lean mass	Baseline
Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of total mass	Baseline
Dual Energy X-ray Absorption (DEXA) Scanning	ND Upper Thigh Lean Mass	Baseline
Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of bone mineral density	Baseline
Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of percent body fat	Baseline
Short Physical Performance Battery (SPPB)	Total Short Physical Performance Battery test score ranging from 0 (worst performance) to 12 (best performance)	Baseline
Short Physical Performance Battery (SPPB) - Chair Stand Test	Chair Stand Test score ranging from 0 (worst performance) to 4 (best performance)	Baseline
Short Physical Performance Battery (SPPB) - Standing Balance Test	Standing Balance Test score ranging from 0 (worst performance) to 4 (best performance)	Baseline
Short Physical Performance Battery (SPPB) - 4 Meter Walk Test	4 Meter Walk Test score ranging from 0 (worst performance) to 4 (best performance)	Baseline
Stair Climb Power Test	Assessment of lower leg power	Baseline
Hand Grip Dynamometry	Assessment of Hand Grip Strength	Baseline
Four Square Test	Assessment of coordination	Baseline
Isometric and Isokinetic Leg Extension Strength	Assessment of isometric and isokinetic leg extonsor strength. Isokinetic leg extensor strength is also used for weakness classification in older adults	Baseline
60-Sec MVC Fatigue Test	Assessment of lower extremity fatigue	Baseline

Collaborators and Investigators

• Sponsor: NMD Pharma A/S
• Collaborators: Ohio State University; Ohio University
• Investigators: Principal Investigator: Brian Clark, PhD, Ohio University

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Actual): September 22, 2021
• Study Completion (Actual): September 22, 2021

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 22, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): November 11, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Neuromuscular Disease; Repetitive Nerve Stimulation; Neuromuscular Junction Transmission; Single Fiber EMG
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: Sarcopenia Observational

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No