Passive Stretching in Peripheral Arterial Disease Patients

Passive Stretching and Dietary Nitrate Rescue Functional Capacity in Peripheral Arterial Disease

Peripheral artery disease (PAD) leads to higher mortality rates and strains healthcare systems due to increased costs. It causes leg pain during walking due to reduced blood flow. Nitric oxide (NO) deficiency contributes to vascular issues in PAD, with few effective treatments available. Passive calf muscle stretching boosts NO levels, vascular health, and walking ability in PAD patients. However, the inflammatory processes underlying these improvements are unclear. This study aims to track inflammatory markers and cardiovascular changes during 12 weeks of passive stretching. Additionally, combining stretching with dietary nitrate could further enhance walking capacity by reducing reactive oxygen species. The study will monitor inflammation, vascular function, and oxidative capacity to understand the effects on functional ability in PAD patients. This research is crucial for improving physical function and addressing exercise intolerance in PAD.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Peripheral Arterial Disease; Walking, Difficulty
• Intervention / Treatment: Device: Calf Plantar flexion; Dietary supplement: Dietary nitrate

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jacob T Caldwell, Ph.D.; Phone Number: 608-785-8684; Email: jcaldwell@uwlax.edu

Study Locations

• United States
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54650
      • Recruiting
      • University of Wisconsin La Crosse
      • Contact: Jacob T Caldwell, Ph.D.; Phone Number: 608-785-8684

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Ankle-brachial index of 0.90 or less Stable condition for at least 3 months

Exclusion Criteria:

Habitual exercise or cardiovascular rehabilitation program during the past 3 months Critical limb ischemia, amputation, or leg pain at rest Major surgery or lower extremity revascularization in the last 3 months Heart Failure Kidney disease Beet alergy Crohn's Current smoker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Functional Walking capacity; Passive stretching of the calf muscles 5 days per week for 12-weeks	Device: Calf Plantar flexion; Daily passive calf stretching; Dietary supplement: Dietary nitrate; Weekday 140 ml dietary nitrate consumption two hours prior to passive stretching
Experimental: Inflammation; Blood and muscle biopsy samples pre/post passive stretching to assess local and systemic inflammation	Device: Calf Plantar flexion; Daily passive calf stretching; Dietary supplement: Dietary nitrate; Weekday 140 ml dietary nitrate consumption two hours prior to passive stretching

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional capacity	6-minute walking distance will be assessed prior to an at various time points during the 12-week study	12-14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory markers	Blood and calf muscle biopsy will be used to assess various inflammatory markers pre/post treatment.	12-14 weeks
Vascular function	Large vessel (flow-mediated vasodilation) and small vessel (Near-infrared spectroscopy on the calf) will be measured prior to and at various time points during the 12-week study.	12-14 weeks

Collaborators and Investigators

• Sponsor: University of Wisconsin, La Crosse
• Investigators: Principal Investigator: Jacob T Caldwell, Ph.D., Assistant Professor

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Cardiovascular
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Inflammation; Peripheral Arterial Disease; Peripheral Vascular Diseases; Mobility Limitation
• Other Study ID Numbers: 232-JC-230.2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study datasets will be submitted to a generalist repository (Aging Research Bio Bank or similar). This allows for individual-level data submission from clinical studies. This study will not generate genomics data and will not submit to the database of Genotypes and Phenotypes. To our understanding, the NIA repository is the only current general repository for aging related work
• IPD Sharing Time Frame: Raw data will be available after two years post data collection to allow for publication and only available for one year after data collection is complete.
• IPD Sharing Access Criteria: Researchers.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No