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Immunonutrition for Diabetic Foot Ulcers

Primary Purpose

Diabetes Mellitus, Diabetic Peripheral Neuropathy, Diabetic Foot Ulcer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lovaza
L-Arginine Powder
Vitamin C
Sponsored by
Prisma Health-Midlands
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • ≥ 18 years of age at the time of informed consent
  • Toe blood pressure (TBP) >40 mmHg
  • Hemoglobin A1c <10% (measured within the previous 6 months)
  • Diagnosis of diabetes mellitus
  • Presence of at least one new chronic, non-healing (present for ≥4 weeks), lower extremity wound (Werner stage 2-3)
  • Documented lipid panel within 3 months of study enrollment
  • Documented CMP within 3 months of study enrollment
  • Documented ECG within 3 months of study enrollment
  • Receiving standard or care defined as sharps debridement, appropriate dressing, and offloading.

Exclusion Criteria:

  • Allergy to fish
  • Current smoker
  • Currently taking any OTC supplements containing Omega-3 fatty acids, L-Arginine, or Vitamin C, or antibiotics
  • Presence of at least one of the following diseases or conditions: End stage renal disease as defined by patients who have been diagnosed with Stage 4 kidney disease and are not on hemodialysis or who are on hemodialysis with a GFR consistently < 15L/min and BUN > 60, Untreated deep bone infection (osteomyelitis), Currently pregnant or breastfeeding
  • Women of child-bearing potential
  • Prisoners and other institutionalized individuals
  • Any patients who have a legal representative to make medical decisions on their behalf or any individuals who are otherwise deemed as medically incompetent.

Sites / Locations

  • Prisma Health

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Standard of Care Group

Immunonutrition Supplementation Group

Arm Description

Patients will receive standard of care wound treatment as determined by a treating physician.

Patients will receive a 6 week daily oral supply of 1.68 grams Omega-3 fatty acids, 4.5 grams L-Arginine, and 500 mg Vitamin C.

Outcomes

Primary Outcome Measures

Effect of supplemental immunonutrition on wound healing in patients with diabetic foot ulcers as assessed by the Pressure Ulcer Scale for Healing (PUSH) Tool 3.0.
The PUSH Tool 3.0 will be used to score ulcers based on size (cm2), exudate amount, and tissue type present. The score ranges for size, exudate amount, and tissue type are 0-10, 0-3, and 0-4, respectively. For all categories, a higher score indicates a more severe ulcer. The score for each category is combined to generate a final score ranging from 0-17. A higher final score indicates a more severe ulcer. The treating physician will record ulcer scores using this tool at the time of consent and biweekly for 6 weeks for both the standard of care group and experimental group.

Secondary Outcome Measures

Effect of supplemental immunonutrition on patient reported pain scores in patients with diabetic foot ulcers.
Patients in both the standard of care and experimental groups will report visual analog scale (VAS) pain scores at the time of consent and weekly in either office visits with the treating physician or via phone calls with a research coordinator. The VAS scale ranges from 0-10, with a higher score indicating a higher level of pain.
Effect of supplemental immunonutrition on patient satisfaction in patients with diabetic foot ulcers.
Patients in experimental group will complete a survey detailing their satisfaction with the supplemental immunonutrition regimen following completion study participation. Patients will be asked to rate their satisfaction from very satisfied to very unsatisfied and questions regarding their likelihood to partake in the same treatment regimen for a subsequent ulcer, recommend this treatment regimen to others, and the level of difficulty associated with taking the supplementation.
Long term effect of supplemental immunonutrition on wound healing in patients with diabetic foot ulcers on rates of ulcer recurrence, infection, surgical intervention, and amputation.
Study participants in both the standard of care and experimental groups will be monitored via chart review for one year following the completion of their 6 week participation in the study to assess recurrence rates of diabetic foot ulcers and to identify rate of infection, surgical intervention, and amputation.

Full Information

First Posted
March 7, 2022
Last Updated
March 20, 2023
Sponsor
Prisma Health-Midlands
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1. Study Identification

Unique Protocol Identification Number
NCT05281562
Brief Title
Immunonutrition for Diabetic Foot Ulcers
Official Title
Effects of Supplemental Immunonutrition on Healing of Chronic Non-Healing Lower Extremity Ulcers in Diabetic Patients: A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
There are not enough patients at our institution meeting eligibility criteria to complete the study as intended.
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
March 20, 2023 (Actual)
Study Completion Date
March 20, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prisma Health-Midlands

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Diabetes-induced peripheral neuropathy can lead to the development of diabetic foot ulcers (DFUs), which can have a devastating effect on patients' lives and can lead to life threatening infection, amputations, and even death. Conventional treatment of DFUs are time consuming, burdensome, costly, and often do not treat the root cause of the problem. Even with proper care, ulcers can take a significantly longer time to heal in diabetic patients due to the altered physiology which does not allow for the proper nutrients and healing factors to mobilize to the site of injury, leaving these ulcers with a poor chance of healing and at high risk for infection and possible amputation. Supplemental immunonutrition therapy may offer a viable, low cost, rapidly scalable, and widely available approach to enhance the body's ability to heal itself. This prospective, randomized pilot study will evaluate the effect of a 6-week daily oral course of a specific combination of immunonutrients, L-Arginine, Omega-3 fatty acids, and Vitamin C, on wound healing in diabetic patients with chronic lower extremity ulcers compared to traditional standard of care. The deliverables of this clinical project will serve to advance a cost-effective added strategy to address a significant unmet clinical need in treatment for the diabetic patient population. Study outcomes will lay the foundation for a multi-site clinical trial to establish the efficacy and cost-effectiveness of this strategy across the health care system.
Detailed Description
Diabetes mellitus is one of the most prevalent chronic diseases in the world and its incidence is expected to increase over the next 20 years. Historically there are three described types of diabetes mellitus: Type 1, Type 2, and Gestational. The etiology of disease may vary between types, and our current understanding notes overlap of these types, yet the resulting pathophysiology is the same: poor peripheral blood flow, decreased cellular response at the injury site, elevated glucose levels, and poor nutrient transport. Despite many of these patients having an elevated Body Mass Index (BMI), they are functionally under or malnourished. In addition, some patients develop progressive neurologic dysfunction, called peripheral neuropathy (PN). A common complication of diabetes induced PN is the development of diabetic foot ulcers (DFUs), which can have a devastating effect on patients' lives and can lead to life threatening infection, amputations, and even death. Conventional treatment of DFUs includes shoe wear modification, self-monitoring, local wound care, brace and shoe offloading, and surgical intervention as well as more sophisticated treatments such as bioengineered cellular technologies and hyperbaric oxygen therapy. These modalities are time consuming, burdensome, costly, and often do not treat the root cause of the problem. Additionally, even with proper care, ulcers can take a significantly longer time to heal in diabetic patients due to the altered physiology which does not allow for the proper nutrients and healing factors to mobilize to the site of injury, leaving these ulcers with a poor chance of healing and at high risk for infection and possible amputation. In contrast to traditional treatment modalities, nutrition therapy has been shown to aide in healing of chronic wounds by providing essential nutrients which were not previously present in necessary amounts in diabetic patients. Nutrition therapy has proven useful in modulating inflammation and the immune response, optimizing glucose control, and attenuating the hypermetabolic response to ulcers, ultimately improving healing and recovery. Thus, supplemental immunonutrition therapy may offer a viable, low cost, rapidly scalable, and widely available approach to enhance the body's ability to heal itself. This prospective, randomized pilot study will evaluate the effect of a 6-week daily oral course of a specific combination of immunonutrients, L-Arginine, Omega-3 fatty acids, and Vitamin C, on wound healing in diabetic patients with chronic lower extremity ulcers compared to traditional standard of care. Wound characteristics and clinical photographs will be documented throughout the course of the study. Patient-reported pain scores, side effects, and unscheduled visits to emergency departments/urgent care centers will be recorded. Patients randomized to receive immunonutrition supplementation will complete an additional survey detailing their satisfaction with the treatment plan upon completion of their participation in the study. The deliverables of this clinical project will serve to advance a cost-effective added strategy to address a significant unmet clinical need in treatment for the diabetic patient population. Study outcomes will lay the foundation for a multi-site clinical trial to establish the efficacy and cost-effectiveness of this strategy across the health care system.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Diabetic Peripheral Neuropathy, Diabetic Foot Ulcer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomized to receive 6 weeks of oral immunonutrition supplementation, consisting of L-Arginine, Vitamin C, and Omega-3 fatty acids, in addition to standard of care for wound treatment or standard of care alone.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care Group
Arm Type
No Intervention
Arm Description
Patients will receive standard of care wound treatment as determined by a treating physician.
Arm Title
Immunonutrition Supplementation Group
Arm Type
Experimental
Arm Description
Patients will receive a 6 week daily oral supply of 1.68 grams Omega-3 fatty acids, 4.5 grams L-Arginine, and 500 mg Vitamin C.
Intervention Type
Drug
Intervention Name(s)
Lovaza
Other Intervention Name(s)
omega-3 fatty acids, omega-3-acid ethyl esters
Intervention Description
Daily dose of 1.68grams omega-3 fatty acids, 2 Lovaza pills per day.
Intervention Type
Drug
Intervention Name(s)
L-Arginine Powder
Other Intervention Name(s)
Arginine, 2-amino-5-guanidinopentanoic acid
Intervention Description
Daily dose of 4.5 grams L-Arginine, powder form.
Intervention Type
Drug
Intervention Name(s)
Vitamin C
Other Intervention Name(s)
Ascorbic acid
Intervention Description
Daily dose of 500 mg Vitamin C, powder form.
Primary Outcome Measure Information:
Title
Effect of supplemental immunonutrition on wound healing in patients with diabetic foot ulcers as assessed by the Pressure Ulcer Scale for Healing (PUSH) Tool 3.0.
Description
The PUSH Tool 3.0 will be used to score ulcers based on size (cm2), exudate amount, and tissue type present. The score ranges for size, exudate amount, and tissue type are 0-10, 0-3, and 0-4, respectively. For all categories, a higher score indicates a more severe ulcer. The score for each category is combined to generate a final score ranging from 0-17. A higher final score indicates a more severe ulcer. The treating physician will record ulcer scores using this tool at the time of consent and biweekly for 6 weeks for both the standard of care group and experimental group.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Effect of supplemental immunonutrition on patient reported pain scores in patients with diabetic foot ulcers.
Description
Patients in both the standard of care and experimental groups will report visual analog scale (VAS) pain scores at the time of consent and weekly in either office visits with the treating physician or via phone calls with a research coordinator. The VAS scale ranges from 0-10, with a higher score indicating a higher level of pain.
Time Frame
6 weeks
Title
Effect of supplemental immunonutrition on patient satisfaction in patients with diabetic foot ulcers.
Description
Patients in experimental group will complete a survey detailing their satisfaction with the supplemental immunonutrition regimen following completion study participation. Patients will be asked to rate their satisfaction from very satisfied to very unsatisfied and questions regarding their likelihood to partake in the same treatment regimen for a subsequent ulcer, recommend this treatment regimen to others, and the level of difficulty associated with taking the supplementation.
Time Frame
6 weeks
Title
Long term effect of supplemental immunonutrition on wound healing in patients with diabetic foot ulcers on rates of ulcer recurrence, infection, surgical intervention, and amputation.
Description
Study participants in both the standard of care and experimental groups will be monitored via chart review for one year following the completion of their 6 week participation in the study to assess recurrence rates of diabetic foot ulcers and to identify rate of infection, surgical intervention, and amputation.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 18 years of age at the time of informed consent Toe blood pressure (TBP) >40 mmHg Hemoglobin A1c <10% (measured within the previous 6 months) Diagnosis of diabetes mellitus Presence of at least one new chronic, non-healing (present for ≥4 weeks), lower extremity wound (Werner stage 2-3) Documented lipid panel within 3 months of study enrollment Documented CMP within 3 months of study enrollment Documented ECG within 3 months of study enrollment Receiving standard or care defined as sharps debridement, appropriate dressing, and offloading. Exclusion Criteria: Allergy to fish Current smoker Currently taking any OTC supplements containing Omega-3 fatty acids, L-Arginine, or Vitamin C, or antibiotics Presence of at least one of the following diseases or conditions: End stage renal disease as defined by patients who have been diagnosed with Stage 4 kidney disease and are not on hemodialysis or who are on hemodialysis with a GFR consistently < 15L/min and BUN > 60, Untreated deep bone infection (osteomyelitis), Currently pregnant or breastfeeding Women of child-bearing potential Prisoners and other institutionalized individuals Any patients who have a legal representative to make medical decisions on their behalf or any individuals who are otherwise deemed as medically incompetent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J. Benjamin Jackson, MD
Organizational Affiliation
Prisma Health-Midlands
Official's Role
Principal Investigator
Facility Information:
Facility Name
Prisma Health
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18801858
Citation
Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008 Nov;88(11):1254-64. doi: 10.2522/ptj.20080020. Epub 2008 Sep 18.
Results Reference
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Citation
Allen L, Powell-Cope G, Mbah A, Bulat T, Njoh E. A Retrospective Review of Adverse Events Related to Diabetic Foot Ulcers. Ostomy Wound Manage. 2017 Jun;63(6):30-33.
Results Reference
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24018732
Citation
Corriere M, Rooparinesingh N, Kalyani RR. Epidemiology of diabetes and diabetes complications in the elderly: an emerging public health burden. Curr Diab Rep. 2013 Dec;13(6):805-13. doi: 10.1007/s11892-013-0425-5.
Results Reference
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PubMed Identifier
31456118
Citation
Hicks CW, Selvin E. Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes. Curr Diab Rep. 2019 Aug 27;19(10):86. doi: 10.1007/s11892-019-1212-8.
Results Reference
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PubMed Identifier
24186882
Citation
Rice JB, Desai U, Cummings AK, Birnbaum HG, Skornicki M, Parsons NB. Burden of diabetic foot ulcers for medicare and private insurers. Diabetes Care. 2014;37(3):651-8. doi: 10.2337/dc13-2176. Epub 2013 Nov 1. Erratum In: Diabetes Care. 2014 Sep;37(9):2660.
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Results Reference
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PubMed Identifier
25371851
Citation
Alexander JW, Supp DM. Role of Arginine and Omega-3 Fatty Acids in Wound Healing and Infection. Adv Wound Care (New Rochelle). 2014 Nov 1;3(11):682-690. doi: 10.1089/wound.2013.0469.
Results Reference
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PubMed Identifier
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Citation
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Results Reference
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Links:
URL
http://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html
Description
National Diabetes Statistics Report, 2020. CDC.
URL
http://www.ncbi.nlm.nih.gov/books/NBK65149/
Description
Incidence of diabetic foot ulcer and lower extremity amputation among Medicare beneficiaries, 2006 to 2008: Data Points #2.

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Immunonutrition for Diabetic Foot Ulcers

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