Venous DiseasePhase 1/2NCT01509599
Cooling Lower Leg Skin to Prevent Venous Leg Ulcers in Patients With Poor Vein Circulation
A Phase 1/2 study testing Cryotherapy: Cooling gel wrap in people with Venous Disease and Venous Vascular Diseases and Syndromes, run by Medical University of South Carolina at 2 sites in United States.
Trial summary
Leg vein circulation problems can damage the skin of the lower legs, especially around the ankles, by making it discolored, hard, itchy, red, and swollen. Ulcers often develop. Inflammation is often present in the damaged skin. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Venous Disease, Venous Vascular Diseases and Syndromes, Venous Insufficiency
- What is being tested?
- Cryotherapy: Cooling gel wrap
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 197 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2011to Dec 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- aged 21 years or older
- CEAP Classification: Stage C4 (skin damage) and 5 (healed VLU) - leg ulcer healed within past month with intact epithelium
- history of healed VLU within past 2 years
- ankle brachial index (ABI) 0.80 - 1.3 mmHG, absence of peripheral arterial disease
- intact skin sensation
- intact thermal sensation
Show all 12Show fewer
- agreement to ear compression during waking hours
- phone, email or mail accessible
- willingness to make 5 study visits including baseline
- able to understand protocol by passing test after watching DVD standardized instructions for low literacy
- able to perform required protocol activities
- ability to speak English
Who cannot join
- diagnosed arterial disease or ABI <0.80 or >1.3 mm Hg (blood flow to the skin is reduced in arterial disease and cooling could cause tissue ischemia)
- surgical procedures on leg in past 1 year (can affect venous circulation/cause edema)
- open leg/foot ulcers
- recent leg infection within past month (increased inflammation)
- impaired cognitive status (cannot perform procedures)
- chronic inflammatory and vascular conditions where blood flow of the skin may be impacted such as Lupus erythematosus, lymphedema, Raynaud's, rheumatoid arthritis, scleroderma, end stage renal disease, chronic obstructive pulmonary disease, chronic regional pain syndrome, multiple sclerosis, hypersensitivity to cold, or patients on chemotherapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Medical University of South Carolina
Charleston, South Carolina, 29425
Spartanburg Regional Medical Center
Spartanburg, South Carolina, 29303
About this study
Official title: Preventing Venous Leg Ulcers With Cryotherapy: A Randomized Clinical Trial
Leg vein circulation problems can damage the skin of the lower legs, especially around the ankles, by making it discolored, hard, itchy, red, and swollen. Ulcers often develop. Inflammation is often present in the damaged skin. This study will test whether using a special low compression, cooling, boot-like gel wrap placed around the damaged skin of the lower legs will improve the skin circulation and prevent leg ulcers. The study hypothesis is: A cryotherapy, low-compression cooling gel wrap (CW) plus usual care (UC) (leg elevation, compression stockings) intervention compared to a low compression non-cryotherapy "sham" wrap (NW) plus UC will reduce tissue blood flow (perfusion units) and decrease the incidence of venous leg ulcers (VLUs) during the 9-month study period in individuals with Stage 4 and 5 venous insufficiency.
Read the detailed description
This new trial will assess the efficacy of this home-based cryotherapy intervention by adding sequenced tapered cooling after a 30-day intense cooling period. The goal is to reduce skin blood flow of chronically inflamed skin, decrease the incidence of venous leg ulcers and pain, and improve quality of life. A myriad of surgical, pharmacologic, and non-pharmacologic therapies such as compression bandages are often tried, many with limited success. More than 70% of patients with venous disorders such as insufficiency develop edema, skin damage, and ulcers. Ulcer prevention is warranted because of the significant socioeconomic implications in terms of lost workdays and wages, decreased productivity and increased health care costs. Clinicians focus on the multiple treatment approaches, often without consideration of how patients can contribute to their own self-care. Our 9-month intervention is based on principles of heat transfer and cryotherapy theories involving microcirculation. With input from a cryotherapy expert and participants who completed the R21 pilot, the investigators propose a sequenced intervention strategy, where cooling will be dosed daily for 30 minutes for the first month, and then decreased to twice weekly dosing in months 2-3, once weekly in months 4-6, then PRN in months 7-9. The investigators will measure blood flow, skin temperature, pain, quality of life, and the incidence of leg ulcers after months 1, 3, 6 and 9. Eligible participants will be randomized to treatment (low compression cooling wrap) or usual care (low compression non-cooling "sham" wrap). Participants in both groups will receive all study related materials including standardized instruction, skin thermometer, specially designed low compression wraps, leg elevator pillow, and compression stockings, and during an in-depth orientation session. The investigators hypothesize that cryotherapy will enhance the largely ineffective non-pharmacologic self-care usual care model, that is, telling patients to wear compression stockings, elevate the legs, and get more exercise. These strategies are generally inadequate in achieving sustained change. Among our research methods the investigators include rigorous process, impact and outcome monitoring. In an era of expectation for technological and pharmaceutical "fixes", this self-care strategy, if efficacious, could be an economical way to decrease morbidity and pain for thousands of patients, frequently viewed as non-responsive to self care. Prevention of ulcers is also a major potential source of saved medical dollars. This trial is significant due to the burden of venous disorders, the complex physical characteristics of the population including excessive obesity and co-morbidity and the need to reach patients with a feasible, motivational, and supportive strategy to promote self-care. The objective is to establish a new practice standard for prevention.
- Conditions
- Venous Disease, Venous Vascular Diseases and Syndromes, Venous Insufficiency, Venous Ulcers
- Being tested
- Cryotherapy: Cooling gel wrap, Usual care
- Keywords
- Venous disease, Venous disorders, Venous insufficiency, Venous ulcers, Cryotherapy
- Medical subject headings
- Syndrome, Venous Insufficiency, Varicose Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cryotherapy: Cooling gel wrapProcedure or surgery
Also called Cooling cuff, cool cuff
Patients will wear compression stockings (provided), elevate legs on an elevator pillow (provided) and apply the sham cyrotherapy: cooling gel wrap during the home-based intervention
Usual careProcedure or surgery
Also called Standard of care, Guideline guided care
Patients will wear compression stockings (provided), elevate legs on an elevator pillow (provided) and apply the sham cyrotherapy wrap (sham) during the home-based intervention
| Study group | Role | What they receive |
|---|---|---|
| Cryotherapy | Experimental | Cryotherapy is delivered via a cooling "gel" wrap applied to the affected lower leg using a dosing regimen, starting with daily cooling in month one to PRN in the last 3 months over the 9 month study. Receives: Procedure: Cryotherapy: Cooling gel wrap |
| Usual care | Sham comparator | The "sham" wrap, filled with cotton, is applied to the affected lower leg using a dosing regimen, starting with daily application in month one to PRN in the last 3 months over the 9 month study. Receives: Procedure: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skin blood flow
Measured: Skin blood flow will be measured for change at five visits: baseline (visit 1), month 1 (visit 2), month 3 (visit 3), month 6 (visit 4) and 9 (visit 5)
Incidence of venous leg ulcers that develop during the study
In the event that a venous leg ulcers develops, the volunteer will notify the study personnel within 24 hours. The volunteer will be instructed to return to the primary care/wound care provider for treatment. Study personnel will contact the volunteer each week to assess progress. If the leg ulcers heals during the time enrolled in the study, the volunteer will continue with the intervention.
Measured: Time point will be assessed at months 1, 3, 6 and 9. If an ulcer develops, participants will be followed weekly, for the duration of the ulcer treatment, up to the end of the study at 9 months.
Secondary outcomes (3)
Quality of life
Measured: During the five measurement points, baseline and then after months, 1, 3, 6, and 9
Pain
Measured: Measured at baseline, then after months 1, 3, 6, and 9
Skin temperature
Measured: Will be measured daily by the subject and then by student personnel at baseline, then after months 1, 3, 6, and 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2012 (estimated)
- Study startAug 2011
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Venous DiseaseStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 197 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Nursing Research (NINR)
- Responsible party
- Principal investigator, Teresa Kelechi, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01509599
- Sponsor's protocol ID
- Pro00008711
- Other IDs
- 1R01NR012237-01A1
- Status last verified
- Apr 2016
- First submitted
- 19 Aug 2011
- Last updated
- 5 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data may be requested via the PI and is available through REDCap.
Publications
Kelechi TJ, Johnson JJ, Yates S. Chronic venous disease and venous leg ulcers: An evidence-based update. J Vasc Nurs. 2015 Jun;33(2):36-46. doi: 10.1016/j.jvn.2015.01.003.
PubMed 26025146Kelechi TJ, Madisetti M, Mueller M, Dooley M, Prentice M. Self-monitoring of lower leg skin temperature: accuracy of self-reported data and adherence to a cooling protocol for the prevention of venous leg ulcers. Patient Prefer Adherence. 2015 Dec 15;9:1751-61. doi: 10.2147/PPA.S91992. eCollection 2015.
PubMed 26719678Kelechi TJ, Mueller M, King DE, Madisetti M, Prentice M. Impact of daily cooling treatment on skin inflammation in patients with chronic venous disease. J Tissue Viability. 2015 May;24(2):71-9. doi: 10.1016/j.jtv.2015.01.006. Epub 2015 Feb 7.
PubMed 25703058Kelechi TJ, Mueller M, Dooley M. Sex differences in symptom severity and clusters in patients with stage C4 and stage C5 chronic venous disease. Eur J Cardiovasc Nurs. 2017 Jan;16(1):28-36. doi: 10.1177/1474515116634526. Epub 2016 Jul 7.
PubMed 26888961Monsen KA, Kelechi TJ, McRae ME, Mathiason MA, Martin KS. Nursing Theory, Terminology, and Big Data: Data-Driven Discovery of Novel Patterns in Archival Randomized Clinical Trial Data. Nurs Res. 2018 Mar/Apr;67(2):122-132. doi: 10.1097/NNR.0000000000000269.
PubMed 29489633
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preventing Venous Leg Ulcers With Cryotherapy: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT01509599
- Acronym / sponsor ID
- Pro00008711
- Conditions
- Venous Disease, Venous Vascular Diseases and Syndromes, Venous Insufficiency, Venous Ulcers
- Keywords
- Venous disease, Venous disorders, Venous insufficiency, Venous ulcers, Cryotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 197 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institute of Nursing Research (NINR)
- Study start
- Aug 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 13 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Leg vein circulation problems can damage the skin of the lower legs, especially around the ankles, by making it discolored, hard, itchy, red, and swollen. Ulcers often develop. Inflammation is often present in the damaged skin. This study will test whether using a special low compression, cooling, boot-like gel wrap placed around the damaged skin of the lower legs will improve the skin circulation and prevent leg ulcers. The study hypothesis is: A cryotherapy, low-compression cooling gel wrap (CW) plus usual care (UC) (leg elevation, compression stockings) intervention compared to a low compression non-cryotherapy "sham" wrap (NW) plus UC will reduce tissue blood flow (perfusion units) and decrease the incidence of venous leg ulcers (VLUs) during the 9-month study period in individuals with Stage 4 and 5 venous insufficiency.
Detailed description
This new trial will assess the efficacy of this home-based cryotherapy intervention by adding sequenced tapered cooling after a 30-day intense cooling period. The goal is to reduce skin blood flow of chronically inflamed skin, decrease the incidence of venous leg ulcers and pain, and improve quality of life. A myriad of surgical, pharmacologic, and non-pharmacologic therapies such as compression bandages are often tried, many with limited success. More than 70% of patients with venous disorders such as insufficiency develop edema, skin damage, and ulcers. Ulcer prevention is warranted because of the significant socioeconomic implications in terms of lost workdays and wages, decreased productivity and increased health care costs. Clinicians focus on the multiple treatment approaches, often without consideration of how patients can contribute to their own self-care. Our 9-month intervention is based on principles of heat transfer and cryotherapy theories involving microcirculation. With input from a cryotherapy expert and participants who completed the R21 pilot, the investigators propose a sequenced intervention strategy, where cooling will be dosed daily for 30 minutes for the first month, and then decreased to twice weekly dosing in months 2-3, once weekly in months 4-6, then PRN in months 7-9. The investigators will measure blood flow, skin temperature, pain, quality of life, and the incidence of leg ulcers after months 1, 3, 6 and 9. Eligible participants will be randomized to treatment (low compression cooling wrap) or usual care (low compression non-cooling "sham" wrap). Participants in both groups will receive all study related materials including standardized instruction, skin thermometer, specially designed low compression wraps, leg elevator pillow, and compression stockings, and during an in-depth orientation session. The investigators hypothesize that cryotherapy will enhance the largely ineffective non-pharmacologic self-care usual care model, that is, telling patients to wear compression stockings, elevate the legs, and get more exercise. These strategies are generally inadequate in achieving sustained change. Among our research methods the investigators include rigorous process, impact and outcome monitoring. In an era of expectation for technological and pharmaceutical "fixes", this self-care strategy, if efficacious, could be an economical way to decrease morbidity and pain for thousands of patients, frequently viewed as non-responsive to self care. Prevention of ulcers is also a major potential source of saved medical dollars. This trial is significant due to the burden of venous disorders, the complex physical characteristics of the population including excessive obesity and co-morbidity and the need to reach patients with a feasible, motivational, and supportive strategy to promote self-care. The objective is to establish a new practice standard for prevention.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cryotherapy | Experimental | Procedure: Cryotherapy: Cooling gel wrapCryotherapy is delivered via a cooling "gel" wrap applied to the affected lower leg using a dosing regimen, starting with daily cooling in month one to PRN in the last 3 months over the 9 month study. |
| Usual care | Sham comparator | Procedure: Usual careThe "sham" wrap, filled with cotton, is applied to the affected lower leg using a dosing regimen, starting with daily application in month one to PRN in the last 3 months over the 9 month study. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- aged 21 years or older
- CEAP Classification: Stage C4 (skin damage) and 5 (healed VLU) - leg ulcer healed within past month with intact epithelium
- history of healed VLU within past 2 years
- ankle brachial index (ABI) 0.80 - 1.3 mmHG, absence of peripheral arterial disease
- intact skin sensation
Key exclusion criteria (6 listed)
- diagnosed arterial disease or ABI <0.80 or >1.3 mm Hg (blood flow to the skin is reduced in arterial disease and cooling could cause tissue ischemia)
- surgical procedures on leg in past 1 year (can affect venous circulation/cause edema)
- open leg/foot ulcers
- recent leg infection within past month (increased inflammation)
- impaired cognitive status (cannot perform procedures)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cryotherapy: Cooling gel wrapAlso: Cooling cuff, cool cuffPatients will wear compression stockings (provided), elevate legs on an elevator pillow (provided) and apply the sham cyrotherapy: cooling gel wrap during the home-based intervention | Procedure or surgery | Cryotherapy |
| Usual careAlso: Standard of care, Guideline guided carePatients will wear compression stockings (provided), elevate legs on an elevator pillow (provided) and apply the sham cyrotherapy wrap (sham) during the home-based intervention | Procedure or surgery | Usual care |
Primary outcome
Skin blood flow
Time frame: Skin blood flow will be measured for change at five visits: baseline (visit 1), month 1 (visit 2), month 3 (visit 3), month 6 (visit 4) and 9 (visit 5)
Incidence of venous leg ulcers that develop during the study
Time frame: Time point will be assessed at months 1, 3, 6 and 9. If an ulcer develops, participants will be followed weekly, for the duration of the ulcer treatment, up to the end of the study at 9 months.
In the event that a venous leg ulcers develops, the volunteer will notify the study personnel within 24 hours. The volunteer will be instructed to return to the primary care/wound care provider for treatment. Study personnel will contact the volunteer each week to assess progress. If the leg ulcers heals during the time enrolled in the study, the volunteer will continue with the intervention.
3 secondary outcomes
Quality of life
Time frame: During the five measurement points, baseline and then after months, 1, 3, 6, and 9
Pain
Time frame: Measured at baseline, then after months 1, 3, 6, and 9
Skin temperature
Time frame: Will be measured daily by the subject and then by student personnel at baseline, then after months 1, 3, 6, and 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2016.
- Background: PubMed 26025146Kelechi TJ, Johnson JJ, Yates S. Chronic venous disease and venous leg ulcers: An evidence-based update. J Vasc Nurs. 2015 Jun;33(2):36-46. doi: 10.1016/j.jvn.2015.01.003.
- Results publication: PubMed 26719678Kelechi TJ, Madisetti M, Mueller M, Dooley M, Prentice M. Self-monitoring of lower leg skin temperature: accuracy of self-reported data and adherence to a cooling protocol for the prevention of venous leg ulcers. Patient Prefer Adherence. 2015 Dec 15;9:1751-61. doi: 10.2147/PPA.S91992. eCollection 2015.
- Results publication: PubMed 25703058Kelechi TJ, Mueller M, King DE, Madisetti M, Prentice M. Impact of daily cooling treatment on skin inflammation in patients with chronic venous disease. J Tissue Viability. 2015 May;24(2):71-9. doi: 10.1016/j.jtv.2015.01.006. Epub 2015 Feb 7.
- Results publication: PubMed 26888961Kelechi TJ, Mueller M, Dooley M. Sex differences in symptom severity and clusters in patients with stage C4 and stage C5 chronic venous disease. Eur J Cardiovasc Nurs. 2017 Jan;16(1):28-36. doi: 10.1177/1474515116634526. Epub 2016 Jul 7.
- Derived from this study: PubMed 29489633Monsen KA, Kelechi TJ, McRae ME, Mathiason MA, Martin KS. Nursing Theory, Terminology, and Big Data: Data-Driven Discovery of Novel Patterns in Archival Randomized Clinical Trial Data. Nurs Res. 2018 Mar/Apr;67(2):122-132. doi: 10.1097/NNR.0000000000000269.
- Individual participant dataSharing planned: Yes. Data may be requested via the PI and is available through REDCap.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cryotherapy: Cooling gel wrap in people with Venous Disease and Venous Vascular Diseases and Syndromes, run by Medical University of South Carolina at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skin blood flow (time frame: Skin blood flow will be measured for change at five visits: baseline (visit 1), month 1 (visit 2), month 3 (visit 3), month 6 (visit 4) and 9 (visit 5)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01509599, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2016.