Clinical trial NCT04791449: Exercise Enhances Wound Healing in Patients With Diabetic Foot Ulcers
Official title: Exercise Enhances Wound Healing in Patients With Diabetic Foot Ulcers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetic Foot Ulcer
Lead sponsor: University of New Mexico
Sponsor class: OTHER
First posted: 2021-03-10
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is based on a two-group repeated measures design.
Primary purpose: TREATMENT

Brief summary: The overarching purpose of this study is to investigate the impact that exercise, as delivered through a medically supervised, outpatient cardiac rehabilitation program, has on the wound healing process in Type 2 diabetics having foot ulcers classified as being Wound, Ischemia, foot Infection (WIfI) stage 2 or lower. The criterion reference measure of diabetic foot ulcer wound healing is be the time required to reach the maturation phase of the wound healing cascade (wound closure without drainage).

Detailed description: This study uses a two-group repeated measures design. Sixty volunteers will be recruited through the University of New Mexico (UNM) Center for Healing in the Lower Extremity (CHILE) clinic. A letter explaining the study will be placed in the file of all diabetic foot ulcer (DFU) clients of CHILE clinic. There is section to be completed by interested clientele (RSVP) and placed it in labelled box in the clinic office.

A research team member collects box contents (M-F) and contacts all respondents using the preferred method provided on the RSVP to conduct an initial screening of inclusion/exclusion criteria and review study requirements. Those not qualifying for the study or uninterested will be thanked for their initial interest. If the respondent is a viable prospect for inclusion, the electronic medical record will be reviewed by the authorized research team member to verify inclusion criteria are satisfied and no exclusion criteria are present. An initial study-related appointment coinciding with their next scheduled wound care appointment at the CHILE clinic will be set for eligible prospects. After screening into the study, the prospects will be randomly assigned to a group via an online randomizer. Group 1 (Treatment as Usual, TAU) participants receive the regularly scheduled standard wound care. Group 2 (Treatment as Usual plus Exercise, TAU-EX) receives the regularly scheduled standard wound care and is assigned to the 12 -week medically supervised exercise program. Body mass index (BMI), HbA1c, weight (wearing similar clothes at each weigh in), and vascular endothelial growth factor (VEGF) levels will be measured at baseline and then again at 4, 8 and 12 weeks.

The Informed Consent will be provided for the prospect's review; questions asked of the research team member are encouraged. The 50:50 likelihood of being randomly assigned to one of two groups (TAU or TAU-EX) will be explained. All participants will receive their regularly scheduled standard wound care (per CHILE Clinic procedures) 2-3 times a week for 12 weeks or until the wound healed if less than 12 weeks. Expectations of group assignment and incentivizing prospects for their time will be discussed fully. If the prospect wants to continue with the study, the Informed Consent will be signed. If the prospect does not want to continue, they will be thanked for their time plus encouraged to continue with their scheduled wound care appointments and follow their wound care professional's recommendations. A Spanish interpreter, in person or via phone, will be used for all subjects who are not fluent in English. Official Spanish language versions of the Consent Form and study questionnaires will be available as well. Regardless of group assignment, the participant will be reminded to continue with their normally scheduled wound care appointments and to follow their wound care professional's recommendations. All participants will also be encouraged to maintain their normal daily activities unless contraindicated by their wound care provider. A typical wound care appointment consists of the CHILE clinic wound care technician removing the dressing. A wound care provider evaluates the drainage and the wound. It is then cleaned with Vashe (Steadme Medical, Fort Worth, TX). The periwound is cleaned with Hibiclens (Molnlycke Health Care, Brooklyn, NY). If debridement is necessary, it is performed by the wound care provider as appropriate for the tissue type and location. Measurement of the wound will be done weekly by the wound care provider using one of two accepted wound measurement methods - clock method or modified clock method. Deviations from the 12:00 - 6:00 numbering scheme are documented for length (i.e 2:00 - 8:00) and width at the widest perpendicular (i.e. 10:00 - 5:00) point to the line of length. Wound depth will be measured at the deepest section and any undermining or tunneling will be referred to by the clock measures. New dressings will be applied.

After giving written consent, the TAU-EX participant will be scheduled for an initial intake session at the UNM Cardiac Rehabilitation facility (ground floor of UNM hospital, UNMH) to review risk factors, current exercise habits, exercise session expectations and undergo a program orientation. They will sign a second consent form, be given a tour of the facility and familiarized with the exercise equipment. They will be reminded that they will be exercising along with cardiac rehabilitation clients in 2 to 3 exercise sessions per week; the sessions will ideally coincide with the TAU-EX participant's normally scheduled wound care appointments. An appointment will be scheduled so the Cardiac Rehabilitation staff can conduct a maximal exercise capacity test per the facility's standard procedure (note: arm-ergometry will be used); the heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), arm cranking cadence and intensity will be converted to MET (metabolic equivalent of task) level(s) with peak MET (MET peak) being the basis for each individualized exercise prescription. Systematic program progression is supervised by the cardiac rehabilitation program staff. Exercise program adjustments to intensity, duration, and modality will be made each session as appropriate and as tolerated by the participant. Exercise-related variables (i.e. intensity, duration, and modality) will be recorded each session. HR and oxygen saturation (O2 sat) will be recorded pre-, during and post exercise. Blood pressure and non-fasting blood glucose will be recorded pre- and post-exercise.

The first exercise session begins with a pre-participation non-fasting blood glucose finger stick, resting HR and BP assessments, a brief (e.g. 5-minute) warm-up on an arm ergometer, and a consult regarding session goals. The exercise physiologist will encourage the participant to exercise in timed bouts at the combination of cadence and resistance equivalent to 50% of MET peak. Each bout is followed by a recovery period (low speed cadence, very light resistance) until HR approaches the pre-exercise level. This is followed by iterations of exertion and active recovery until 20-30 minutes have passed. Following the last bout's active recovery period and seated rest for hemodynamic assessment, the exercise physiologist records all session data, comments, observations, and reviews the session with the participant before scheduling the next exercise session. All subsequent exercise sessions begin with a pre-participation finger stick (blood glucose target range is 100-250 mg/dL), resting hemodynamic assessment, brief warm-up, and consult. Together the exercise physiologist and participant set new goals for the day's session (i.e. increase cadence by 10 rpm at same resistance, exercise at the RPE associated with a slightly higher intensity, add 20 seconds to the exercise bout for the session, etc.). The participant's physiological responses are monitored to ensure safety and recorded for use in upcoming sessions. Exercise prescriptions will be progressed based on individual tolerance, adaptation, and motivation.

Standard wound care appointments consist of removal of wound dressing, evaluation of wound (e.g. drainage, tissue status), wound cleaning, debridement as necessary, measurement, redressing, and offloading (e.g. total contact casting), as applicable. Over the 12-wk intervention period, all participants will be instructed to continue their normal daily routines and adherence to the podiatrist's recommendations. The blood glucose range of 100-250 mg/dL is the acceptable range for the participant to be able to begin the day's exercise program. If the glucose is above or below that range and the participant is symptomatic, the clinic staff will contact the designated research team member who will contact the participant's primary care provider and either refer them to their services or direct the staff to take them to the UNM Urgent Care Clinic. If the participant is asymptomic, the clinic staff will contact the designated research team member and she will discuss the options with the participant regarding going home and re-adjusting meals, medication, or whatever seemed to be the problem and have the participant return to exercise in 1-2 days.

Volunteers may withhold participation or withdraw from the study at any time without impact on their DFU wound care at the CHILE clinic; coverage of TAU-EX exercise sessions will cease. Participants may be withdrawn from the study by research team members if instructions are repeatedly ignored or the participant is deemed at risk for harming themselves if they continue. Upon withdrawal from the study, any hard copy information will be placed in a locked medical records bin that is destroyed in accordance with UNM hospital regulations for destroying all patient information. Data collected prior to withdrawal will remain in the study database and may not be removed until 6 years after the study is completed.

As with any type of exercise, there are risks of injury, loss of consciousness, heart attack and death. Unaccustomed increases in HR, breathing rate, and sweating during exercise sessions, self-consciousness when exercising in a small group, and muscle soreness are all normal responses to exercise. Development of an infection may or may not be associated with the exercise program. All in the TAU-EX group will have provided documentation indicating their medical provider approved of their participation. TAU-EX members will be counseled regarding the warning signs and symptoms of heart attacks, shortness of breath, and/or loss of consciousness.

All exercise sessions will be supervised by the exercise physiologists of the UNMH cardiac rehabilitation program; symptoms indicative of cardiometabolic distress will result in stoppage or intensity reduction of the exercise session. Participants in the TAU and TAU-EX groups may experience bruising, soreness, bleeding, fainting as a result of blood draws and discomfort resulting from the wound care appointments. Finger sticks for the TAU-EX group may result in localized discomfort and/or bruising. DFU wound care is part of each participant's normal treatment plan and beyond the scope of this study.

There may be no direct benefit for individuals participating in this study. However, some people have experienced weight loss, improved blood glucose control, and faster wound healing when exercising on a regular basis. On a larger scale, results from this study may inform the treatment plan of individuals receiving medical care for DFUs.

Based on the nature of the research and the data that will collected, The investigators may find that adherence to the wound care appointment schedules are increased for those in the TAU-EX group compared to TAU. The investigators may also find that adherence may be predicted based on some of the response combinations recorded on the questionnaires (i.e. support of partner, transportation, comradery developed during exercise sessions).

Eligibility criteria: Inclusion Criteria:

* diagnosis of type 2 diabetes
* 20 - 80 years of age
* Ankle-Brachial Index (ABI) \> 0.6 or Toe Pressure (TcPO2) \> 40 mmHg
* recent (within 12 weeks) blood glucose value between 100 - 350 mg/dL
* recent (within 12 weeks) HbA1c value \< 14 %,
* DFU of WIfI Grade 2 or less
* fluency in reading and speaking English or Spanish.

Exclusion Criteria:

* inability to provide own consent
* inability to obtain permission to participate from a medical professional
* lack of consistent mode of transportation to UNMH
* infection to any part of the body
* patients that has had a transplant and/or is immunocompromised
* prisoners.

Primary outcomes:
measure: wound healing time
timeFrame: 12 weeks or less
Secondary outcomes:
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: UNM Cardiac Rehabilitation Services
state: New Mexico
Study officials:
affiliation: University of New Mexico Health Sciences Center
name: Eric J Lew, DPM
role: PRINCIPAL_INVESTIGATOR
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