Spinal Cord InjuryIBSCINCT05319522

The Relationship Between Irisin and Bone Health in Individuals With Spinal Cord Injury

A study testing Acute Exercise in people with Spinal Cord Injury, run by VA Office of Research and Development at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will examine the relationship between circulating irisin and bone health individuals with spinal cord injury. Additionally, this study seeks to examine the influence of muscle fiber type on circulating irisin and identify an exercise-based means to increase irisin concentrations. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Spinal Cord Injury
What is being tested?: Acute Exercise
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 1 siteUnited States
Study dates: 5 May 2023to 30 Apr 2025
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Participants with SCI:
age 18 years or older
traumatic SCI at the cervical level 4 or lower that occurred at least 12 months prior to the start of the study
American Spinal Injury Association Impairment Scale A, B or C
uses a manual wheelchair as primary means of mobility (30+ hours per week)
is able to perform a transfer independently to and from a wheelchair

Show all 9Show fewer

has adequate strength and upper extremity function to operate an arm ergometer
Control Participants:
age and sex-matched to participant with SCI

Who cannot join

Participants with SCI:
active use of medications which potentially affect bone metabolism, including: parathyroid hormone and analogs, androgenic or estrogenic steroids, bisphosphonates, oral glucocorticoids (use for more than 3 months)
history of fractures or dislocations in the upper extremity from which the participant has not fully recovered
upper limb pain or injury that interferes with the ability to perform aerobic exercise
recent hospitalization for any reason (within the past three months)
history of coronary artery disease, coronary bypass surgery or other cardiorespiratory events or conditions

Show all 22Show fewer

likely to experience clinically significant autonomic dysreflexia and/ or orthostatic hypotension in response to vigorous exercise
endocrinopathy or metabolic disorders of the bone
e.g. Paget's disease, renal bone disease
history of allergic reaction to lidocaine
any other conditions that the person's primary care physician deems is a contraindication to participation in arm ergometry exercise stress testing or vigorous exercise
pregnant
participation in another "Greater than Minimal Risk" study.
Control Participants:
active use of medications which potentially affect bone metabolism, including: parathyroid hormone and analogs, androgenic or estrogenic steroids, bisphosphonates, oral glucocorticoids (use for more than 3 months)
history of neuromuscular conditions which could influence muscle gene expression
history of lower body musculoskeletal injuries from which the participant has not fully recovered
recent hospitalization for any reason (within the past three months)
history of allergic reaction to lidocaine
any other conditions that the person's primary care physician deems is a contraindication to the performance of a vastus lateralis muscle biopsy
pregnant
participation in another "Greater than Minimal Risk" study

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Pittsburgh, Pennsylvania, 15240

Other trials in United States

About this study

Official title: The Influence of Irisin/FNDC5 on Bone Mineral Density and Fracture Risk in Individuals With Spinal Cord Injury

Read the detailed description

After spinal cord injury (SCI), the severe sub-lesion bone loss increases lower-limb fracture risk. In addition to mechanical loading, bone homeostasis is mediated by myokines, skeletal muscle secreted factors, including irisin. This project aims to demonstrate that irisin is a key determinant of bone mineral density in sub-lesion bone, that impaired irisin mechanisms contribute to post-SCI bone loss, and identify novel modalities to leverage the osteogenic effects of irisin to improve musculoskeletal rehabilitation strategies for individuals with SCI.

The first aim of this project seeks to determine the relationship between circulating irisin and bone mineral density (BMD) in sub-lesion bones of individuals with SCI. Past research has reported positive correlations between irisin and BMD indicating that irisin is important factor in bone homeostasis. To date, the relationship between irisin and BMD, absent mechanical loading, as seen in individuals with SCI, has not been examined. Of note, irisin increases have been demonstrated to increase bone mass in healthy mice and prevent or reduce bone loss in mouse SCI models.

The second aim of this study seeks to determine if irisin concentrations are impaired as a result of pathologic changes in sub-lesion skeletal muscle after SCI. Irisin is released into circulation following cleavage of its precursor protein which is highly expressed in skeletal muscle. Generally, healthy human muscle demonstrates a mix of type I and type II muscle fibers, however, after SCI, there is a pathological transformation from type I to type II muscle. Given that irisin's precursor protein is more highly expressed in type I muscle, the post-SCI fiber type transformation could significantly attenuate circulating irisin concentrations and impair its downstream signaling effects. Understanding whether post-SCI fiber type shifts are associated with reduced circulating irisin could help explain the inefficacy of current rehabilitation methods.

The third aim of this study seeks to measure the irisin response to arm ergometer high intensity interval exercise. If circulating irisin concentrations are important to bone health, as current research suggests, then identifying a means in increase circulating irisin is essential to developing better musculoskeletal rehabilitation methods. While exercise has been demonstrated to increase circulating irisin, the exercise modalities performed (running, whole body resistance training) are not feasible for individuals with SCI. Arm ergometry exercise could provide a means to increase circulating concentrations of this osteogenic factor.

Conditions: Spinal Cord Injury
Being tested: Acute Exercise
Keywords: Spinal cord injuries, Irisin, Bone mineral density, Exercise
Medical subject headings: Spinal Cord Injuries, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Acute ExerciseBehavioural
Also called Arm Ergometer Exercise; High-Intensity Interval Exercise
Participants with and without SCI will complete an arm ergometer, high-intensity interval exercise bout. The exercise bout will be performed at a relative intensity based on previously determined peak power output during an arm ergometer graded exercise test.

Study groups in NCT05319522
Study group	Role	What they receive
Individuals with SCI	Active comparator	Male and female, Veteran and non-Veteran participants with traumatic SCI will complete the baseline blood draw, muscle biopsy and DXA/HR-pQCT bone imaging. This group will complete blood draws before and after arm ergometer high-intensity interval exercise bout. Receives: Behavioral: Acute Exercise
Controls (No SCI)	Active comparator	Male and female Veterans, age and sex-matched to participants with SCI will complete the baseline blood draw, muscle biopsy and DXA/HR-pQCT bone imaging. This group will complete blood draws before and after arm ergometer high-intensity interval exercise bout. Receives: Behavioral: Acute Exercise

What is being measured

The primary outcome is the main question the study is designed to answer.

Irisin-Trabecular vBMD Correlation
Circulating irisin concentration correlated with trabecular volumetric bone mineral density at the distal tibia (4% site) in individuals with SCI and controls
Measured: Baseline; at rest
Irisin-Cortical vBMD Correlation
Circulating irisin concentration correlated with cortical volumetric bone mineral density at the distal tibia (30% site) in individuals with SCI and controls
Measured: Baseline; at rest
Irisin-Bone Failure Load Correlation
Circulating irisin concentration correlated with bone failure load at the distal tibia (4% site) in individuals with SCI and controls
Measured: baseline; at rest
Irisin-Bone Failure Load Correlation
Circulating irisin concentration correlated with bone failure load at the distal tibia (30% site) in individuals with SCI and controls
Measured: baseline; at rest
Irisin-Cortical Porosity Correlation
Circulating irisin concentration correlated with cortical porosity at the distal tibia (30% site) in individuals with SCI and controls
Measured: baseline; at rest
FNDC5 Gene Expression
Vastus lateralis skeletal muscle FNDC5 gene expression relative to beta-2-microglobulin (ΔΔCt)
Measured: Baseline; at rest
Exercise Induced Change in Irisin Concentration
Circulating irisin concentrations will be measured before and immediately following an arm ergometer high-intensity interval exercise bout
Measured: Baseline (resting) to immediately post-acute exercise bout (~22 minutes later)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 May 202330 Apr 2025

First posted8 Apr 2022
Study start5 May 2023
Primary completion30 Apr 2025
Study completion30 Apr 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Spinal Cord InjuryStudies of the same condition, open and under way.
More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05319522
Sponsor's protocol ID: B3641-M
Acronym: IBSCI
Status last verified: Aug 2026
First submitted: 31 Mar 2022
Last updated: 1 Sep 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Influence of Irisin/FNDC5 on Bone Mineral Density and Fracture Risk in Individuals With Spinal Cord Injury
ClinicalTrials.gov ID: NCT05319522
Acronym / sponsor ID: IBSCI / B3641-M
Conditions: Spinal Cord Injury
Keywords: Spinal cord injuries, Irisin, Bone mineral density, Exercise
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: VA Office of Research and DevelopmentUS federal agency
Study start: 5 May 2023 (actual)
Primary completion: 30 Apr 2025 (actual)
Study completion: 30 Apr 2025 (actual)
First posted: 8 Apr 2022 (actual)
Results: Posted 1 Sep 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Individuals with SCI	Active comparator	Behavioral: Acute ExerciseMale and female, Veteran and non-Veteran participants with traumatic SCI will complete the baseline blood draw, muscle biopsy and DXA/HR-pQCT bone imaging. This group will complete blood draws before and after arm ergometer high-intensity interval exercise bout.
Controls (No SCI)	Active comparator	Behavioral: Acute ExerciseMale and female Veterans, age and sex-matched to participants with SCI will complete the baseline blood draw, muscle biopsy and DXA/HR-pQCT bone imaging. This group will complete blood draws before and after arm ergometer high-intensity interval exercise bout.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

age 18 years or older
traumatic SCI at the cervical level 4 or lower that occurred at least 12 months prior to the start of the study
American Spinal Injury Association Impairment Scale A, B or C
uses a manual wheelchair as primary means of mobility (30+ hours per week)
is able to perform a transfer independently to and from a wheelchair

Key exclusion criteria (22 listed)

active use of medications which potentially affect bone metabolism, including: parathyroid hormone and analogs, androgenic or estrogenic steroids, bisphosphonates, oral glucocorticoids (use for more than 3 months)
history of fractures or dislocations in the upper extremity from which the participant has not fully recovered
upper limb pain or injury that interferes with the ability to perform aerobic exercise
recent hospitalization for any reason (within the past three months)
history of coronary artery disease, coronary bypass surgery or other cardiorespiratory events or conditions

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Acute ExerciseAlso: Arm Ergometer Exercise; High-Intensity Interval ExerciseParticipants with and without SCI will complete an arm ergometer, high-intensity interval exercise bout. The exercise bout will be performed at a relative intensity based on previously determined peak power output during an arm ergometer graded exercise test.	Behavioural	Controls (No SCI), Individuals with SCI

Primary outcome

Irisin-Trabecular vBMD Correlation
Time frame: Baseline; at rest
Circulating irisin concentration correlated with trabecular volumetric bone mineral density at the distal tibia (4% site) in individuals with SCI and controls
Irisin-Cortical vBMD Correlation
Time frame: Baseline; at rest
Circulating irisin concentration correlated with cortical volumetric bone mineral density at the distal tibia (30% site) in individuals with SCI and controls
Irisin-Bone Failure Load Correlation
Time frame: baseline; at rest
Circulating irisin concentration correlated with bone failure load at the distal tibia (4% site) in individuals with SCI and controls
Irisin-Bone Failure Load Correlation
Time frame: baseline; at rest
Circulating irisin concentration correlated with bone failure load at the distal tibia (30% site) in individuals with SCI and controls
Irisin-Cortical Porosity Correlation
Time frame: baseline; at rest
Circulating irisin concentration correlated with cortical porosity at the distal tibia (30% site) in individuals with SCI and controls
FNDC5 Gene Expression
Time frame: Baseline; at rest
Vastus lateralis skeletal muscle FNDC5 gene expression relative to beta-2-microglobulin (ΔΔCt)
Exercise Induced Change in Irisin Concentration
Time frame: Baseline (resting) to immediately post-acute exercise bout (~22 minutes later)
Circulating irisin concentrations will be measured before and immediately following an arm ergometer high-intensity interval exercise bout

Results and safety

Results posted to the registry on 1 Sep 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Individuals With SCI	8	5
Controls (No SCI)	3	3

Primary outcome: Irisin-Trabecular vBMD Correlation

Time frame: Baseline; at rest. Number. Unit: Pearson Correlation Coefficient

Measure	Individuals With SCI n = 5	Controls (No SCI) n = 3
Value	0.178	-0.999

Individuals With SCI: p = 0.822, Bivariate correlation
Controls (No SCI): p = 0.020, Bivariate correlation

Population analysed: The correlations were analyzed separately for the Individuals with SCI group and the Controls group. Analyses were intended to determine if the correlation between the trabecular vBMD and irisin was significant in each group, not to compare the correlations between groups. Given the sample size of the Controls group (n=3), the results should be interpreted with caution.

Primary outcome: Irisin-Cortical vBMD Correlation

Time frame: Baseline; at rest. Number. Unit: Pearson Correlation Coefficient

Measure	Individuals With SCI n = 5	Controls (No SCI) n = 3
Value	0.833	0.026

Individuals With SCI: p = 0.080, Bivariate correlation
Controls (No SCI): p = 0.984, Bivariate correlation

Population analysed: The correlations were analyzed separately for the Individuals with SCI group and the Controls group. Analyses were intended to determine if the correlation between the cortical vBMD and irisin was significant in each group, not to compare the correlations between groups. Given the sample size of the Controls group (n=3), the results should be interpreted with caution.

Primary outcome: Irisin-Bone Failure Load Correlation

Time frame: baseline; at rest. Number. Unit: Pearson Correlation Coefficient

Measure	Individuals With SCI n = 5	Controls (No SCI) n = 3
Value	-0.432	-0.999

Individuals With SCI: p = 0.467, Bivariate correlation
Controls (No SCI): p = 0.031, Bivariate correlation

Population analysed: The correlations were analyzed separately for the Individuals with SCI group and the Controls group. Analyses were intended to determine if the correlation between the bone failure load and irisin was significant in each group, not to compare the correlations between groups. Given the sample size of the Controls group (n=3), the results should be interpreted with caution.

Primary outcome: Irisin-Bone Failure Load Correlation

Time frame: baseline; at rest. Number. Unit: Pearson Correlation Coefficient

Measure	Individuals With SCI n = 5	Controls (No SCI) n = 3
Value	-0.265	-0.986

Individuals With SCI: p = 0.667, Bivariate correlation
Controls (No SCI): p = 0.106, Bivariate correlation

Population analysed: The correlations were analyzed separately for the Individuals with SCI group and the Controls group. Analyses were intended to determine if the correlation between the bone failure load and irisin was significant in each group, not to compare the correlations between groups. Given the sample size of the Controls group (n=3), the results should be interpreted with caution.

Adverse events

Time frame: From enrollment until visit 2 follow-up (approximately 48-72 hours later post-visit 2), an average of 15 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Individuals With SCI	2 of 8 (25%)	0 of 8 (0%)	0 of 8
Controls (No SCI)	0 of 3 (0%)	0 of 3 (0%)	0 of 3

Limitations and caveats (from the sponsor): Enrollment in the individuals with SCI and control groups were lower than anticipated, limiting interpretation of the results of this investigation. Due to the small size of the control group, the investigators were not able to examine correlations between irisin and bone outcomes. Skeletal muscle yields from the microbiopsy technique were lower than anticipated. Thus, there insufficient tissue to perform muscle fiber type analyses following the gene expression analyses.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Adam J. Sterczala, PhD principal investigator

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Acute Exercise in people with Spinal Cord Injury, run by VA Office of Research and Development at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Irisin-Trabecular vBMD Correlation (time frame: Baseline; at rest). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05319522.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.