Improving Mobility and Function Following Transfemoral Amputation: A Novel Approach to Reverse Volumetric Muscle Loss

The purpose of this study is to investigate the relationship between thigh strength and walking ability and assess if using a blood pressure cuff on the leg improves strength and walking performance.

Study Overview

• Status: Not yet recruiting
• Conditions: Traumatic Amputation of Lower Extremity
• Intervention / Treatment: Other: Ischemic Preconditioning

Detailed Description

One in every 190 Americans is currently living with the loss of a limb. Following lower limb amputation (LLA), individuals have double the risk of knee and hip pain, a high prevalence of osteoarthritis in the intact limb with a prevalence ratio of 3.3 compared to those without amputation, and up to 90% experience severe back pain. The long-term consequences of LLA may be mitigated through regular use of prosthesis and physical activity, which would also increase the likelihood of returning to work and reintegration of Service Members (SMs) and younger Veterans.

Clinicians and researchers often focus on the prosthetic fit to improve outcomes, however just providing a prosthetic, even the most advanced prosthetic, is not enough to restore function. Interventions targeting physical capabilities to complement device intervention may be key to improving outcomes in individuals with LLA.

Along with increased orthopaedic risks, individuals with traumatic LLA also have an increased risk of cardiovascular events compared to the general population. SMs with traumatic unilateral transfemoral amputation have a 1.58 times greater risk of death from cardiovascular causes and their relative risk of aortic aneurysm is 5.1 times greater than Veterans without amputation. There is evidence to suggest that individuals with LLA have increased peripheral vascular resistance following amputation, leading to vasoconstriction and increased blood pressure. Reduced arterial function (i.e. increased arterial stiffness) is an important measure in those with LLA because it predicts mortality, heart failure, and cardiovascular events. In addition, improved arterial function improves perfusion to muscle and reduces fatigue during exertion. Therefore, strategies that reduce arterial stiffness and vascular resistance in individuals with LLA are important to improve mortality and quality of life for SMs and Veterans.

Therefore, we propose implementing ischemic preconditioning (IC) as a novel intervention to strengthen and hypertrophy leg muscles and increase arterial function for improving outcomes after amputation.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lindsay Slater; Phone Number: 3123558965; Email: slaterlv@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least 18 years old
• History of lower limb unilateral transfemoral amputation.
• At least two years post lower limb amputation
• Able to ambulate independently without the use of aids (i.e., walking cane).
• Able to walk at least 10 minutes continuously without stopping.
• Has a safe residuum with no open wounds on either the residual or intact limb.
• Has a prosthetic limb with materials that are sound and safe to withstand the mobility requirements of the study.

Exclusion Criteria:

• Younger than 18 years old.
• Inability to give informed consent.
• Neurological disorder that affects gait.
• Participants with significant metal (greater than one orthopaedic screw) in either the residual limb or the sound/intact limb
• Participants who begin taking medications or change dosage of medications that could affect gait, balance, and cardiovascular function during the course of the study.
• Currently pregnant (or intend to become pregnant while participating in study).
• History of any condition where fatiguing contractions or resisted leg contractions are contraindicated.
• Blood clots in the leg, or any condition in which compression of the thigh or transient ischemia is contraindicated (e.g. open wounds in the leg).
• History of uncontrolled hypertension.
• History of heart failure.
• Head injury within the previous 6 months.
• Seizure disorder.
• History of vascular disease.
• History of thrombosis.
• History of sickle cell trait.
• History of genetic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ischemic Preconditioning at High Pressure; In this arm, the participant will receive ischemic preconditioning (a blood pressure cuff on the intact limb) inflated to 225mmHg for 5 minutes followed by 5 minutes of reperfusion on a cycle for a total of 50 minutes. This will be completed every other day for 7 session (14 days).	Other: Ischemic Preconditioning; A blood pressure cuff will be placed on the thigh of the intact/sound limb to restrict blood flow to the lower extremity for 5 minutes and then deflated for 5 minutes to allow for normal blood flow on a cycle for 50 minutes (5 times).
Sham Comparator: Ischemic Preconditioning at Low Pressure; In this arm, the participant will receive ischemic preconditioning (a blood pressure cuff on the intact limb) inflated to 25mmHg for 5 minutes followed by 5 minutes of reperfusion on a cycle for a total of 50 minutes. This will be completed every other day for 7 session (14 days).	Other: Ischemic Preconditioning; A blood pressure cuff will be placed on the thigh of the intact/sound limb to restrict blood flow to the lower extremity for 5 minutes and then deflated for 5 minutes to allow for normal blood flow on a cycle for 50 minutes (5 times).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Strength	Comparing leg strength before and after intervention	through study completion, an average of 6 weeks
Gait	Comparing leg strength before and after intervention	through study completion, an average of 6 weeks
Metabolics	Comparing leg strength before and after intervention	through study completion, an average of 6 weeks
Daily Steps/Activity	Comparing leg strength before and after intervention	through study completion, an average of 6 weeks
Arterial Stiffness	Comparing leg strength before and after intervention	through study completion, an average of 6 weeks

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Lindsay Slater, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 16, 2023
• First Submitted That Met QC Criteria: June 26, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Amputation, Traumatic
• Other Study ID Numbers: 2023-0250

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