Prehabilitation of Frail Surgical Cancer Patients Using Remote Ischemic Preconditioning (Prehab)

• ClinicalTrials.gov Identifier: NCT03853473
• Recruitment Status: Recruiting
• First Posted: February 25, 2019
• Last Update Posted: October 15, 2021
• Sponsor: Medical College of Wisconsin
• Information provided by (Responsible Party): Matthew Durand, Medical College of Wisconsin

Study Description

Brief Summary:

This project will examine the efficacy of a simple, cost-effective, non-invasive intervention, called remote ischemic preconditioning (RIPC), to reduce frailty in pre-surgical, frail, elderly patients with colon cancer. The investigators hypothesize that RIPC will reduce frailty in the pre-surgical period (as assessed by distance walked during the 6-minute walk test), improve functional capacity 4-weeks postoperatively, and reduce intraoperative blood pressure variability. If successful, future studies will examine the efficacy of RIPC to improve surgical outcomes in frail cancer patients.

Condition or disease	Intervention/treatment	Phase
Colon Cancer; Fragility; Prehabilitaiton; Surgery	Procedure: Remote Ischemic Preconditioning	Not Applicable

Detailed Description:

Remote ischemic preconditioning (RIPC) was first described three decades ago as an intervention to protect vital organs from ischemic injury. RIPC occurs when a tissue is made transiently ischemic (5 minutes) for repeated bouts (5 times) prior to the longer ischemic insult. Recently it has been shown exercise performance and motor function are improved in young, healthy individuals when RIPC is performed on the arm or leg using a simple blood pressure cuff to occlude blood flow to the limb. The application of RIPC to individuals with reduced functional capacity, however, is largely unexplored. The study team was the first to apply RIPC to chronic stroke survivors with reduced physical function, and two weeks of RIPC increases walking speed, paretic muscle strength and fatigue resistance. Advanced age and cancer are both dramatic accelerators of frailty and frail patients have poor surgical outcomes. Therefore, the investigators propose to apply this non-invasive, simple intervention as a "prehabiliative" therapy to elderly patients with colon cancer during the perioperative period. The investigators will enroll 96 colon cancer patients aged 55-85 who are ≥17 days prior to scheduled curative resection of colon cancer. After study enrollment, all participants will perform the six-minute walk test as a measure of frailty. Participants will then be randomized to receive either RIPC on their upper, non-dominant arm daily for 14 days prior to surgery, or to receive standard of care (no intervention). After 14 days of either RIPC or no intervention, the 6-minute walk test will be re-assessed within 48 hours of surgery. The primary study outcome will be the difference in six-minute walk distance (in meters) between patients in the RIPC group vs. those in the standard of care group following the two-week pre-operative intervention period (Aim 1). The investigators hypothesize that patients in the RIPC group will walk further during the six-minute walk test than those in the standard of care group due to the well-defined effects of RIPC to improve athletic performance, cardiovascular function, and strength in healthy individuals. A secondary study outcome will be the difference in six-minute walk test distance between the RIPC and standard of care group 4-weeks postoperatively (Aim 2). The investigators hypothesize that patients in the RIPC group will have more rapid recovery from surgery, which would be evidenced by increased walking endurance post-operatively. Another secondary study outcome will be the amount of intraoperative blood pressure variability (time systolic pressure is above or below 135 mmHg or 95 mmHg, respectively) between the RIPC and control groups (Aim 3). The investigators hypothesize that RIPC will reduce intraoperative blood pressure variability due to the well described effects of RIPC to improve systemic vascular function. Future larger studies will examine the effects of RIPC prehabilitation on surgical outcomes such as length of hospital stay and all-cause mortality in frail, elderly patients with colon cancer as well as other patient cohorts with reduced functional capacity.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, Randomized, Blinded, Controlled Trial
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Participants are randomized by the study statistician to receive either the intervention (remote ischemic conditioning) or standard of care. Participants cannot be blinded using this model.
• Primary Purpose: Treatment
• Official Title: Prehabilitation of Frail Surgical Cancer Patients Using Remote Ischemic Preconditioning
• Actual Study Start Date: February 22, 2019
• Estimated Primary Completion Date: February 21, 2024
• Estimated Study Completion Date: February 21, 2024

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Standard of Care; Study participants will receive standard of care.
Experimental: Remote Ischemic Preconditioning; Study participants will perform remote ischemic preconditioning daily, at home, from study enrollment to their date of surgery.	Procedure: Remote Ischemic Preconditioning; Remote Ischemic Preconditioning (RIPC) occurs when a limb is made transiently ischemic (5 minutes) using a simple blood pressure cuff. We are proposing that study participants in the RIPC group perform the intervention daily at home for at least 14 days prior to scheduled surgery. They will inflate a blood pressure cuff on the upper portion of their nondominant arm, inflate it to 225 mmHg for 5 minutes, release the cuff for 5 minutes, and repeat this 5 times (for a total of 45 minutes). A study coordinator will monitor compliance with phone calls and daily log sheets that must be filled out.

Outcome Measures

Primary Outcome Measures :

1. 6 Minute Walk Test Distance (Pre Surgery) [ Time Frame: Years 1-3 ]
   The investigators will compare the distance study participants can walk in 6 minutes in the pre-surgical period as a measure of frailty.

Secondary Outcome Measures :

1. 10 Meter Walk Test (Pre Surgery) [ Time Frame: Years 1-3 ]
   The investigators will compare the speed study participants walk over 10 meters in the pre-surgical period as a secondary measure of frailty.
2. Timed Up and Go (Pre Surgery) [ Time Frame: Years 1-3 ]
   The investigators will compare the speed study participants stand from a chair, walk three meters, turn around, walk back to the chair, and sit (timed up and go test) in the pre-surgical period as a secondary measure of frailty.
3. Hand Grip Strength (Pre Surgery) [ Time Frame: Years 1-3 ]
   The investigators will compare handgrip strength in the presurgical period as a secondary measure of frailty.
4. 6 Minute Walk Test Distance (Post Surgery) [ Time Frame: Years 1-3 ]
   The investigators will compare the distance study participants walk in 6-minutes 4-weeks post-surgery as a secondary outcome of surgical recovery.
5. 10 Meter Walk Test (Post Surgery) [ Time Frame: Years 1-3 ]
   The investigators will compare the speed study participants walk 10 meters 4-weeks post-surgery as a secondary outcome of surgical recovery.
6. Timed Up and Go (Post Surgery) [ Time Frame: Years 1-3 ]
   The investigators will compare the speed study participants stand from a chair, walk three meters, turn around, walk back to the chair, and sit (timed up and go test) 4-weeks post surgery as a secondary measure of surgical recovery.
7. Hand Grip Strength (Post Surgery) [ Time Frame: Years 1-3 ]
   The investigators will compare handgrip strength 4-weeks post surgery as a secondary measure of surgical recovery.
8. Intraoperative Blood Pressure Variability [ Time Frame: Years 1-3 ]
   The investigators will measure the variability of blood pressure during the intraoperative period using the anesthetic record.

Other Outcome Measures:

1. Number of Hours of Rehabilitation [ Time Frame: Years 1-3 ]
   The investigators will document the number of hours of physical therapy each study participant participates in following surgery.
2. All Cause Mortality [ Time Frame: Years 1-3 ]
   The investigators will document any deaths that occur during hospitalization following surgery.
3. Length of Hospital Stay [ Time Frame: Years 1-3 ]
   The investigators will document how long participants in both study groups (RIPC or standard of care) stay in the hospital following surgery.

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Be between the ages of 55-85
• Have a positive diagnosis of colon cancer or suspected colon cancer based on pathology report
• Be scheduled for curative resection of non-metastatic colon cancer
• Have a 6MWT distance ≤80% of predicted value based on age and sex.

Exclusion Criteria:

• Condition which prevents walking
• Any condition in which compression of the arm or transient ischemia is contraindicated (e.g. wounds in the arm)
• Neurodegenerative disorder
• Unstable angina in previous month
• MI during previous month.

Contacts and Locations

Contacts

Contact: Sahar Ali, BS; 414-805-5495; saali@mcw.edu

Contact: Jennifer Nguyen, BS; 414-779-1317; jnguyen@mcw.edu

Locations

United States, Wisconsin

Medical College of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Matthew J Durand, Ph.D. 414-955-5619 mdurand@mcw.edu

Sponsors and Collaborators

Medical College of Wisconsin

Investigators

• Principal Investigator: Matthew J Durand, Ph.D.; Medical College of Wisconsin
• Principal Investigator: Julie K Freed, MD, Ph.D.; Medical College of Wisconsin

More Information

• Responsible Party: Matthew Durand, Assistant Professor, Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT03853473
• Other Study ID Numbers: PRO00032510
• First Posted: February 25, 2019
• Last Update Posted: October 15, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colonic Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases