Telmisartan Plus Exercise to Improve Functioning in Peripheral Artery Disease

Study Overview
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Brief Summary
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The TELEX trial will establish whether telmisartan alone improves walking performance in people with peripheral artery disease (PAD). The TELEX trial will also determine whether telmisartan plus supervised exercise improves walking performance more than either therapy alone. TELEX is a randomized controlled clinical trial (2 x 2 factorial design) of 112 participants with PAD randomized to one of four arms: Group A: telmisartan + supervised exercise therapy; Group B: telmisartan + a no exercise control group; Group C: placebo + supervised exercise therapy; and Group D: placebo + a no exercise control group.

Official Title
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Telmisartan Plus Exercise to Improve Functioning in Peripheral Artery Disease

Conditions
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Peripheral Artery Disease

Intervention / Treatment
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* Behavioral: Supervised Treadmill Exercise Therapy
* Drug: Telmisartan
* Other: No exercise control group
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants will have PAD. PAD will be defined as follows. First, an ABI <= 0.90 at the baseline study visit is an inclusion criterion for PAD. Second, potential participants who have an ABI > 0.90 but ≤ 1.00 and experience a 20% or higher drop in ABI after heel-rise exercise will be eligible. Third, potential participants with an ABI > 0.90 who have vascular lab evidence of PAD or angiographic evidence of PAD will be eligible. Finally, potential participants with a history of lower extremity revascularization who do not meet the criterion above and have an ABI > 0.90 with a 20% or higher drop in ABI after heel-rise exercise will be eligible. Exclusion Criteria: Above or below knee amputation, critical limb ischemia, wheelchair confinement, inability to walk without a walker, or current foot ulcer. Walking is limited by a condition other than PAD. > Class II NYHA heart failure or angina, increase in angina, angina at rest, or abnormal baseline treadmill stress test. Potential participants may become eligible following an abnormal baseline treadmill stress test if they have evidence of an absence of coronary ischemia based on testing with their own physician. Currently taking an angiotensin receptor blocker or an ACE inhibitor or use of these medications in the past three months. Currently taking aliskiren (Tekturna). Blood pressure < 100/50 at baseline or potassium > 5.0 meq/L at baseline. Blood pressure < 100/50 after run-in or potassium >= 5.5 meq/L at the end of run-in. Severe hepatic impairment defined by two or more liver function enzyme values greater than 2.5 the upper limit of normal. Acute decline in renal function on telmisartan, defined as a 30% or greater decline in eGFR following the two-week run-in as compared to baseline. If the participant had a baseline eGFR performed by his/her physician within two months of the baseline eGFR for the TELEX trial, the participant's physician's eGFR may be considered the baseline measure, at the study principal investigator's discretion. Allergy to ARBs. Failure to successfully complete the 2-week study run-in, defined as failing to attend the health education and treadmill exercise run-in sessions and/or failing to take the study medication daily for 10 or more days in the two-week period (i.e. one pill per day for > 10 days out of the 14 day run-in period). Surgery including lower extremity revascularization, coronary revascularization with stenting, or orthopedic surgery during the past 3 months or anticipated in the next 6 months or myocardial infarction or stroke in the past 3 months. Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. [NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who only use oxygen at night may still qualify.] MMSE score < 23 or dementia. Currently walking regularly for exercise at a level similar to the study intervention. Participation in another clinical trial or cardiac rehabilitation or completion of a clinical trial or cardiac rehabilitation in the previous three months. [NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing an exercise intervention or a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.] Non-English speaking, a visual impairment that limits walking ability, or a hearing impairment that interferes with study participation. Congestive heart failure with an ejection fraction <40. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Telmisartan + Supervised Treadmill Exercise Therapy<br>Participants in this group will receive both daily telmisartan and supervised treadmill exercise three days weekly for six months. | Behavioral: Supervised Treadmill Exercise Therapy<br>* Participants randomized to the exercise intervention will receive supervised treadmill exercise three times weekly for six months.<br>* Other names: Treadmill exercise;Drug: Telmisartan<br>* Participants randomized to the telmisartan arm of the study will take 20 mg or 40 mg of telmisartan daily based on the results of their study run-in. Participants will have their dose increased to up to 80 mg as tolerated.<br>* Other names: Micardis;|
| Active Comparator: Telmisartan + No Exercise Control Group<br>Participants in this group will receive daily telmisartan and attend weekly educational lectures at the medical center for six months. | Drug: Telmisartan<br>* Participants randomized to the telmisartan arm of the study will take 20 mg or 40 mg of telmisartan daily based on the results of their study run-in. Participants will have their dose increased to up to 80 mg as tolerated.<br>* Other names: Micardis;Other: No exercise control group<br>* Participants randomized to the attention control group will attend weekly one-hour educational sessions at Northwestern University for six months.<br>* Other names: Attention control group;|
| Active Comparator: Placebo + Supervised Treadmill Exercise Therapy<br>Participants randomized to this group will receive daily placebo and supervised treadmill exercise three times weekly for six months. | Behavioral: Supervised Treadmill Exercise Therapy<br>* Participants randomized to the exercise intervention will receive supervised treadmill exercise three times weekly for six months.<br>* Other names: Treadmill exercise;Drug: Placebo<br> <br> |
| Placebo Comparator: Placebo + No Exercise Control Group<br>Participants randomized to this group will receive daily placebo and health education lectures weekly for six months. | Other: No exercise control group<br>* Participants randomized to the attention control group will attend weekly one-hour educational sessions at Northwestern University for six months.<br>* Other names: Attention control group;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-minute Walk Performance | We will determine whether telmisartan therapy with or without exercise improves six-minute walk distance at 6-month follow-up, compared to placebo with or without exercise (i.e. two group comparisons of all participants randomized to telmisartan vs. all participants randomized to placebo). | Change from baseline to six-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Treadmill Walking Distance | In the treadmill walking test, participants walk on either a gardner or modified gardner protocol until they stop the test. Distance walked is recorded. | Change from baseline to six-month follow-up | 
| Walking Impairment Questionnaire (WIQ) Distance Score | The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. | Change from baseline to six-month follow-up | 
| SF-36 Physical Functioning Score | The SF-36 physical functioning score will be used to measure quality of life. They are scored on a 0-100 scale and that 100 indicates the best possible score. | Change from baseline to six-month follow-up | 
| Walking Impairment Questionnaire (WIQ) Speed Score | The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. | Change from baseline to six-month follow-up | 
| Walking Impairment Questionnaire (WIQ) Stair-climbing Score | The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed and stair-climbing. They are scored on a 0-100 scale and that 100 indicates the best possible score. | Change from baseline to six-month follow-up |