Investigating Loss of Neuromuscular Junction Transmission Fidelity in Older Adults

Sarcopenia Clinical Trial

— STAMINA  

Official title:

Investigating Loss of Neuromuscular Junction Transmission Fidelity in Older Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04904926
• Other study ID #: Sarcopenia Observational
• Status: Completed
• Start date: March 16, 2021
• Est. completion date: September 22, 2021

Study information

• Verified date: November 2021
• Source: NMD Pharma A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: September 22, 2021
• Est. primary completion date: September 22, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sarcopenia

Locations

Country	Name	City	State
United States	Ohio University	Athens	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
NMD Pharma A/S	Ohio State University, Ohio University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Magnetic Resonance Imaging	Assessment of thigh muscle cross-sectional area	Baseline
Secondary	Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of appendicular lean mass	Baseline
Secondary	Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of total lean mass	Baseline
Secondary	Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of total mass	Baseline
Secondary	Dual Energy X-ray Absorption (DEXA) Scanning	ND Upper Thigh Lean Mass	Baseline
Secondary	Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of bone mineral density	Baseline
Secondary	Dual Energy X-ray Absorption (DEXA) Scanning	Assessment of percent body fat	Baseline
Secondary	Short Physical Performance Battery (SPPB)	Total Short Physical Performance Battery test score ranging from 0 (worst performance) to 12 (best performance)	Baseline
Secondary	Short Physical Performance Battery (SPPB) - Chair Stand Test	Chair Stand Test score ranging from 0 (worst performance) to 4 (best performance)	Baseline
Secondary	Short Physical Performance Battery (SPPB) - Standing Balance Test	Standing Balance Test score ranging from 0 (worst performance) to 4 (best performance)	Baseline
Secondary	Short Physical Performance Battery (SPPB) - 4 Meter Walk Test	4 Meter Walk Test score ranging from 0 (worst performance) to 4 (best performance)	Baseline
Secondary	Stair Climb Power Test	Assessment of lower leg power	Baseline
Secondary	Hand Grip Dynamometry	Assessment of Hand Grip Strength	Baseline
Secondary	Four Square Test	Assessment of coordination	Baseline
Secondary	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
Secondary	60-Sec MVC Fatigue Test	Assessment of lower extremity fatigue	Baseline