A Phase 4 interventional study of Ramipril in Peripheral Arterial Disease, sponsored by University of Nebraska. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by University of Nebraska · Phase 4, Interventional, and Treatment
Peripheral artery disease (PAD) is a manifestation of atherosclerosis that produces progressive narrowing and occlusion of the arteries supplying the lower extremities. The most common clinical manifestation of PAD is claudication, i.e., a severe functional limitation identified as gait dysfunction and walking-induced leg muscle pain relieved by rest. The standard therapies for claudication include the medications cilostazol and pentoxifylline, supervised exercise therapy and operative revascularization. Recent data demonstrated that 24 weeks of treatment with the angiotensin-converting enzyme (ACE) inhibitor Ramipril produces improvements in the walking performance of patients with claudication that are higher than those of cilostazol and pentoxifylline and similar to those produced by supervised exercise therapy and operative revascularization. The mechanisms by which Ramipril therapy produces this impressive improvement in the functional capacity of claudicating patients remain unknown. The Investigators hypothesize that treatment of claudicating PAD patients with Ramipril will improve walking performance and quality of life by improving the myopathy of the gastrocnemius. Improved myopathy is a consequence of reduced oxidative damage, reduced TGF-β1 production by vascular smooth muscle cells and reduced collagen deposition in the affected gastrocnemius.
This is an interventional study of PAD patients that exhibit claudication. The purpose of this study is to determine the potential mechanisms by which Ramipril vastly improves the walking performance of these patients. The study will be achieved through these specific aims:
Specific Aim #1: Test the hypothesis that Ramipril-mediated improvements of walking parameters among patients with PAD correlate with improvements in both the morphometrics and biochemistry of myofibers in the gastrocnemius of the impaired limb.
Specific Aim #2: Test the hypothesis that Ramipril-mediated improvements of walking parameters in patients with PAD correlate with reduced fibrotic events in small vessels and microvasculature, in association with reduced generalized collagen deposition and improved tissue oxygenation, in the gastrocnemius of the impaired limb.
Specific Aim #3: Using adult human arterial smooth muscle cells (AHASMC), in vitro, the Investigators will test the hypothesis that the ACE inhibitor Ramipril, which acts as an antagonist of Angiotensin II type 1 receptor (ART1) stimulation by reducing tissue Angiotensin II (Ang II), impedes a mechanism in which Ang II stimulation of ART1 and exposure to hypoxia enhance proliferation of AHASMC and their production of TGF-β1 and collagen, via stimulation of phosphoinositide-3-kinase signaling and suppression of phosphatase and tensin homologue, a master regulator of cell growth.
If the above hypotheses are correct, Aims #1 and #2 will demonstrate for the first time that therapy with Ramipril improves the walking performance and quality of life of claudicating PAD patients by improving the myopathy in skeletal muscle of the ischemic lower limbs. The work in Aim #3 will determine the pathways by which hypoxia and Angiotensin II cooperate to induce myopathy in the ischemic muscle. Specific agents targeting these pathways could become new treatments for claudication and for the more advanced stages of PAD characterized by leg rest pain and gangrene.
1,377 studies on the registry are indexed under Peripheral Arterial Disease; 275 are open to participants now.
This study's planned enrollment of 70 is close to the median of 70 across 927 interventional studies indexed under Peripheral Arterial Disease.
Browse Peripheral Arterial Disease studies →University of Nebraska is the lead sponsor of 496 studies on the registry; 67 are open to participants now.
Of its 83 completed or terminated interventional studies of FDA-regulated products, 53 (64%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
6 months treatment with the medication Ramipril
Drug: Ramipril
Ramipril therapy will start at 2.5mg/day for 1 week. Then 5mg/day for 1 week and will be increased to 10mg/day by the third week. The patients will stay on Ramipril 10mg/day for 22 weeks.
Also known as: Altace
Absolute Claudication Distance
Maximum walking distance in meters per Gardner protocol
Time frame: 6 months
6-minute Walking Distance
Maximum Distance in meters the patient can walk in 6 minutes on a flat, hard surface
Time frame: 6 months
Initial Claudication Distance
The distance in meters the patient can walk before he experiences claudication pain, per Gardner protocol
Time frame: 6 months
Average Daily Steps Taken
Monitored with an accelerometer at home
Time frame: 6 months
Quality of life measured by the Walking Impairment Questionnaire
There are 14 questions across three categories of walking distance, walking speed and stair climbing. The WIQ is graded on a scale of 0-4; 0 represents no difficulty; 4 represents inability to walk. 0 score represents no difficulty, 1 score is slight difficulty, 2 score is some difficulty, 3 score is much difficulty, 4 score is unable to complete the task in question.
Time frame: 6 months
Quality of life measured by the Medical Outcomes Study Short Form 36 Healthy Survey
\- (The Short Form 36 Health Survey Questionnaire) has 8 scale (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health) that measures quality of life. The SF-36 scoring ranges from 0-100. Higher scores indicate better health; lower scores indicate more disability
Time frame: 6 months
Leg biomechanics measured as Vertical ground reaction force
measured as Vertical ground reaction force
Time frame: 6 months
Leg hemodynamics measured as Ankle Brachial Index (ABI)
Ratio of the blood pressure at the level of the ankle to the blood pressure at the level of the arm
Time frame: 6 months
Leg hemodynamics
measured as Calf blood flow via contrast-enhanced ultrasound
Time frame: 6 months
Leg hemodynamics measured as Calf blood flow via stress ABI testing
measured as Calf blood flow via stress ABI testing
Time frame: 6 months
Leg hemodynamics measured as Calf muscle hemoglobin oxygen saturation
Measured with Near Infrared Spectroscopy
Time frame: 6 months
Myofiber Mitochondrial Respiration, measured by polarography
measured by polarography
Time frame: 6 months
Muscle Mitochondrial Function, measured by spectrophotometry
measured by spectrophotometry
Time frame: 6 months
Myofiber Oxidative Damage
Myofiber content of HNE adducts and protein carbonyls
Time frame: 6 months
Myofiber Morphology, Cross-Sectional Area
Area in square microns, measured by immunofluorescence microscopy
Time frame: 6 months
Myofiber Morphology, Roundness
Measured as ratio of major axis in microns to minor axis in microns
Time frame: 6 months
Myofiber Morphology, Solidity
Measured as the ratio of myofiber area in square microns to the area of a fitted convex hull in square microns
Time frame: 6 months
Muscle Fibrosis, Muscle TGF-β1
Measured as the sum of the products of mean pixel intensity (in gray scale units) and area (in square microns) of each TGF-β1 labeled event divided by the total area (in square microns) of the tissue sample analyzed. Measured by immunofluorescence microscopy.
Time frame: 6 months
Muscle Fibrosis, Total collagen deposited.
Measured as the area-weighted mean pixel intensity (in gray scale units) of all the collagen labeled events per tissue sample. Measured by bright-field microscopy.
Time frame: 6 months
Microvascular Fibrosis, Capillary wall thickness.
Measured in microns by immunofluorescence microscopy of vessels labeled for collagen.
Time frame: 6 months
Capillary density.
Number of capillaries per unit area (in square microns) of the tissue sample analyzed.
Time frame: 6 months
Serum biomarker of fibrosis, serum procollagen type I c-peptide in picograms of peptide per ml
serum procollagen type I c-peptide in picograms of peptide
Time frame: 6 months
Serum biomarker of fibrosis, serum procollagen type III n-terminal peptide in picograms of peptide per ml
serum procollagen type III n-terminal peptide in picograms of peptide per ml
Time frame: 6 months
Plasma biomarker of fibrosis, plasma TGF-β1 in picograms per ml
plasma TGF-β1 in picograms per ml
Time frame: 6 months
Plan to share: No
No publications or documents are linked to this record.
Started Feb 2016 (actual). Primary completion is estimated for Jun 2027, 136 months after the start.
Of 28 phase 4 interventional studies under Peripheral Arterial Disease, half reached primary completion within 35 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 56. This study's planned 136 months is above that.
Since we started tracking on Sep 25, 2026, the dates moved once, on Oct 23, 2026: primary completion Jun 2026 → Jun 2027 and completion Jun 2026 → Jun 2027.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Ramipril