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CompletedNCT03435835Updated Aug 30, 2022Results posted

Heat Therapy to Reduce Pain and Improve Walking Tolerance

An interventional study of Control/Sham Treatment and Heat Therapy (HT) in Peripheral Arterial Disease, sponsored by Indiana University. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2022-08-30.

Sponsored by Indiana University · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
19
Allocation
Randomized
Sex
All
01

Study summary

The purpose of this study is to investigate whether exposure to heat therapy improves calf muscle oxygenation and enhances walking tolerance in patients with symptomatic Peripheral Arterial Disease (PAD).

Read the detailed description

Heat therapy (HT) is an emerging non-invasive approach that has been shown to enhance vascular function of the leg in old individuals. The objective of this study is to establish evidence to support the validity of HT in improving walking tolerance on PAD patents.

Subjects will complete baseline assessments for eligibility, including medical history and ankle-brachial measurement. Eligible participants will be asked to report to the laboratory on 4 different occasions. The purpose of visits 1 and 2 The central hypothesis of this study, based on preliminary data, is that exposure to HT will enhance the oxygenation of calf muscles during exercise and as a result, the onset of pain will be delayed and walking performance will be enhanced. is to familiarize the participants with the treadmill walking test and assess the test-retest reliability of maximal walking time determination. On visits 3 and 4 participants will receive either heat treatment or a control treatment for 80 min prior to undergoing a symptom-limited incremental test on the treadmill.

02

Conditions studied

03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Men and women with stable symptomatic leg claudication for 6 months or longer.
  • Ankle brachial index \< 0.9

Exclusion criteria

Exclusion Criteria:

  • Heart Failure
  • COPD
  • Critical limb ischemia
  • Prior amputation
  • Exercise-limiting co-morbidity
  • Recent infrainguinal revascularization or planned during study period
  • Plans to change medical therapy during duration of the study
  • Active cancer
  • Chronic kidney disease
  • HIV positive, active HBV or HCV disease
  • Presence of any unsuitable comorbid clinical condition in the opinion of the PI
  • Peripheral neuropathy, numbness or paresthesia in the legs
  • Morbid obesity, BMI > 36 or unable to fit in water-circulating pants
  • Open wounds or ulcers on the extremity
  • Unable to walk on the treadmill
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
19 participants (actual)

Study arms

  • Experimental
    Sham, then heat therapy

    Participants were fitted with liquid-circulating trousers. In the sham-treatment session, water at 33℃ was circulated through the trousers for 90 min using a water pump (HTP-1500, Adroit Medical, Louden, Tennessee, United States). At least 72 hrs after completion of the sham treatment session, participants returned to the laboratory and received the heat therapy (HT) treatment. In the HT session, water at 43℃ was circulated through the tube-lined trousers using a heated bath circulator (HT; Aqua Relief Systems, Akron, Ohio, United States) with the goal of increasing leg skin temperature to 37-38ºC.

    Device: Control/Sham Treatment · Device: Heat Therapy (HT)

  • Experimental
    Heat therapy, then sham

    Participants were fitted with liquid-circulating trousers. In the HT session, water at 43℃ was circulated through the tube-lined trousers using a heated bath circulator (HT; Aqua Relief Systems, Akron, Ohio, United States) with the goal of increasing leg skin temperature to 37-38ºC. At least 72 hrs after completion of the sham treatment session, participants returned to the laboratory and received the sham treatment. In the sham-treatment session, water at 33℃ was circulated through the trousers for 90 min using a water pump (HTP-1500, Adroit Medical, Louden, Tennessee, United States).

    Device: Control/Sham Treatment · Device: Heat Therapy (HT)

Interventions

  • DeviceControl/Sham Treatment

    Water at 33ºC was circulated through water-circulating trousers.

  • DeviceHeat Therapy (HT)

    Water at 42-43ºC was circulated through the water-circulating trousers.

05

What researchers measure

Primary outcomes

  1. Peak Walking Time

    Exercise testing was performed in a motorized treadmill (Pro 27, Woodway, St. Paul, Minnesota, United States) following the Gardner-Skinner protocol, which consists of walking at a constant speed (2 mph) with a 2%-grade increase every 2 min (Gardner et al., 1991). Participants received standardized instructions and were asked to indicate when they first began to feel leg pain with a "thumbs up" signal (defined as COT), and then give a "thumbs down" signal when they could no longer continue with the test (defined as PWT).

    Time frame: Immediately after exposure to a single session of heat therapy or sham treatment, up to ~20 min

Secondary outcomes

  1. Claudication Onset Time

    Exercise testing was performed in a motorized treadmill (Pro 27, Woodway, St. Paul, Minnesota, United States) following the Gardner-Skinner protocol, which consists of walking at a constant speed (2 mph) with a 2%-grade increase every 2 min (Gardner et al., 1991). Participants received standardized instructions and were asked to indicate when they first began to feel leg pain with a "thumbs up" signal (defined as COT), and then give a "thumbs down" signal when they could no longer continue with the test (defined as PWT).

    Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min

  2. Peak Systolic Blood Pressure

    Blood pressure was measured in the left arm using a stethoscope and sphygmomanometer during exercise.

    Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min

  3. Peak Diastolic Blood Pressure

    Blood pressure was measured in the left arm using a stethoscope and sphygmomanometer prior and during exercise

    Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min

  4. Peak Calf Tissue Saturation Index

    The tissue saturation index (TSI%) of the most symptomatic leg was assessed with a commercially available NIRS system (Portamon, Artinis Medical Systems, The Netherlands).

    Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min

  5. Post-exercise Plasma Endothelin-1 Concentration

    Commercially available enzyme-linked immunosorbent assay kits were used to measure the plasma concentrations of ET-1 (DET100, Endothelin-1 Quantikine ELISA Kit, R\&D Systems, Minneapolis, MN, United States)

    Time frame: The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min. Ten minutes following completion of the incremental treadmill test, blood samples were obtained for the assessment of serum ET-1

06

Results

Posted Aug 30, 2022

Participant flow

Participants were identified and contacted by the Indiana Clinical and Translational Science Institute Research Network (ResNet) research assistants. After interest in participation was established, patients were contacted directly by the investigators. Additional study participants were identified by physicians from the Division of Vascular Surgery at Methodist Hospital.

First Intervention
Participant flow — First Intervention
MilestoneSham, Then Heat TherapyHeat Therapy, Then Sham
Started88
Completed88
Not completed00
Washout
Participant flow — Washout
MilestoneSham, Then Heat TherapyHeat Therapy, Then Sham
Started88
Completed88
Not completed00
Second Intervention
Participant flow — Second Intervention
MilestoneSham, Then Heat TherapyHeat Therapy, Then Sham
Started88
Completed88
Not completed00

Outcome measures

PrimaryPeak Walking Time

Exercise testing was performed in a motorized treadmill (Pro 27, Woodway, St. Paul, Minnesota, United States) following the Gardner-Skinner protocol, which consists of walking at a constant speed (2 mph) with a 2%-grade increase every 2 min (Gardner et al., 1991). Participants received standardized instructions and were asked to indicate when they first began to feel leg pain with a "thumbs up" signal (defined as COT), and then give a "thumbs down" signal when they could no longer continue with the test (defined as PWT).

Time frame:
Immediately after exposure to a single session of heat therapy or sham treatment, up to ~20 min
Reported as:
Mean · seconds
Peak Walking Time
secondsSham TreatmentHeat Therapy
Peak Walking Time955.6 ± 84.3947.7 ± 88.1
SecondaryClaudication Onset Time

Exercise testing was performed in a motorized treadmill (Pro 27, Woodway, St. Paul, Minnesota, United States) following the Gardner-Skinner protocol, which consists of walking at a constant speed (2 mph) with a 2%-grade increase every 2 min (Gardner et al., 1991). Participants received standardized instructions and were asked to indicate when they first began to feel leg pain with a "thumbs up" signal (defined as COT), and then give a "thumbs down" signal when they could no longer continue with the test (defined as PWT).

Time frame:
The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min
Reported as:
Mean · Seconds
Claudication Onset Time
SecondsSham TreatmentHeat Therapy
Claudication Onset Time452.6 ± 53.2442.9 ± 65.1
SecondaryPeak Systolic Blood Pressure

Blood pressure was measured in the left arm using a stethoscope and sphygmomanometer during exercise.

Time frame:
The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min
Reported as:
Mean · mmHg
Peak Systolic Blood Pressure
mmHgSham TreatmentHeat Therapy
Peak Systolic Blood Pressure193.3 ± 23.2189.3 ± 31.0
SecondaryPeak Diastolic Blood Pressure

Blood pressure was measured in the left arm using a stethoscope and sphygmomanometer prior and during exercise

Time frame:
The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min
Reported as:
Mean · mmHg
Peak Diastolic Blood Pressure
mmHgSham TreatmentHeat Therapy
Peak Diastolic Blood Pressure74.2 ± 9.773.5 ± 11.6
SecondaryPeak Calf Tissue Saturation Index

The tissue saturation index (TSI%) of the most symptomatic leg was assessed with a commercially available NIRS system (Portamon, Artinis Medical Systems, The Netherlands).

Time frame:
The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min
Reported as:
Mean · % tissue saturation
Peak Calf Tissue Saturation Index
% tissue saturationSham TreatmentHeat Therapy
Peak Calf Tissue Saturation Index43.9 ± 7.643.1 ± 8.2
SecondaryPost-exercise Plasma Endothelin-1 Concentration

Commercially available enzyme-linked immunosorbent assay kits were used to measure the plasma concentrations of ET-1 (DET100, Endothelin-1 Quantikine ELISA Kit, R\&D Systems, Minneapolis, MN, United States)

Time frame:
The exercise test was performed immediately after exposure to a single session of either heat therapy or sham, up to ~20 min. Ten minutes following completion of the incremental treadmill test, blood samples were obtained for the assessment of serum ET-1
Reported as:
Mean · pg/mL
Post-exercise Plasma Endothelin-1 Concentration
pg/mLSham TreatmentHeat Therapy
Post-exercise Plasma Endothelin-1 Concentration2.0 ± 0.61.7 ± 0.5

Adverse events

Collected over Throughout the duration of the study (approximately 1 month).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sham Treatment0/16 (0%)0/16 (0%)1/16 (6.3%)
Heat Therapy0/16 (0%)0/16 (0%)1/16 (6.3%)
Most frequent other events
Most frequent other events
EventSham TreatmentHeat Therapy
HypokalemiaBlood and lymphatic system disorders1/160/16
HypotensionVascular disorders0/161/16

Baseline characteristics

Nineteen participants were consented, but three were withdrawn before receiving an experimental treatment due to inability to safely and consistently perform the treadmill exercise test. Baseline clinical characteristics of the 16 participants that completed all study visits are presented.

Age, Continuous
Age, Continuous(years)All Study Participants
Mean65.7 ± 5.7
Sex: Female, Male
Sex: Female, Male(Participants)All Study Participants
Female2
Male14
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Study Participants
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American4
White12
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(Participants)All Study Participants
United States16
07

Study locations

1 site
  • Indiana University
    Indianapolis, Indiana 46202, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jan 28, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03435835
Lead sponsor
Indiana University
Collaborators
Roseguini, Bruno, PhD, Michael Emery, MD
Responsible party
Raghu Motaganahalli (Associate Professor, Indiana University) — Principal investigator
First posted
Feb 19, 2018
Start date
Aug 1, 2018
Primary completion
Aug 14, 2019
Completion
Aug 14, 2019
Results posted
Aug 30, 2022
Last update
Aug 30, 2022

Study contacts

Raghu L Motaganahalli, MD
principal investigator · Indiana University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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