Immunonutrition for Diabetic Foot Ulcers

NCT ID: NCT05281562

Last Updated: 2024-12-27

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-08

Study Completion Date

2023-03-20

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus Diabetic Peripheral Neuropathy Diabetic Foot Ulcer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard of Care Group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Immunonutrition Supplementation Group

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.

Group Type EXPERIMENTAL

Lovaza

Intervention Type DRUG

Daily dose of 1.68grams omega-3 fatty acids, 2 Lovaza pills per day.

L-Arginine Powder

Intervention Type DRUG

Daily dose of 4.5 grams L-Arginine, powder form.

Vitamin C

Intervention Type DRUG

Daily dose of 500 mg Vitamin C, powder form.

Interventions

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Lovaza

Daily dose of 1.68grams omega-3 fatty acids, 2 Lovaza pills per day.

Intervention Type DRUG

L-Arginine Powder

Daily dose of 4.5 grams L-Arginine, powder form.

Intervention Type DRUG

Vitamin C

Daily dose of 500 mg Vitamin C, powder form.

Intervention Type DRUG

Other Intervention Names

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omega-3 fatty acids omega-3-acid ethyl esters Arginine 2-amino-5-guanidinopentanoic acid Ascorbic acid

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prisma Health-Midlands

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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J. Benjamin Jackson, MD

Role: PRINCIPAL_INVESTIGATOR

Prisma Health-Midlands

Locations

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Prisma Health

Columbia, South Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 18801858 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28657897 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24018732 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31456118 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24186882 (View on PubMed)

Evans DC, Martindale RG, Kiraly LN, Jones CM. Nutrition optimization prior to surgery. Nutr Clin Pract. 2014 Feb;29(1):10-21. doi: 10.1177/0884533613517006. Epub 2013 Dec 17.

Reference Type BACKGROUND
PMID: 24347529 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25371851 (View on PubMed)

Zhang XJ, Chinkes DL, Wolfe RR. The anabolic effect of arginine on proteins in skin wound and muscle is independent of nitric oxide production. Clin Nutr. 2008 Aug;27(4):649-56. doi: 10.1016/j.clnu.2008.01.006. Epub 2008 Mar 7.

Reference Type BACKGROUND
PMID: 18316142 (View on PubMed)

Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011 Sep 1;51(5):1000-13. doi: 10.1016/j.freeradbiomed.2011.05.017. Epub 2011 May 25.

Reference Type BACKGROUND
PMID: 21664268 (View on PubMed)

Cereda E, Klersy C, Serioli M, Crespi A, D'Andrea F; OligoElement Sore Trial Study Group. A nutritional formula enriched with arginine, zinc, and antioxidants for the healing of pressure ulcers: a randomized trial. Ann Intern Med. 2015 Feb 3;162(3):167-74. doi: 10.7326/M14-0696.

Reference Type BACKGROUND
PMID: 25643304 (View on PubMed)

Leigh B, Desneves K, Rafferty J, Pearce L, King S, Woodward MC, Brown D, Martin R, Crowe TC. The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers. J Wound Care. 2012 Mar;21(3):150-6. doi: 10.12968/jowc.2012.21.3.150.

Reference Type BACKGROUND
PMID: 22399084 (View on PubMed)

Desneves KJ, Todorovic BE, Cassar A, Crowe TC. Treatment with supplementary arginine, vitamin C and zinc in patients with pressure ulcers: a randomised controlled trial. Clin Nutr. 2005 Dec;24(6):979-87. doi: 10.1016/j.clnu.2005.06.011. Epub 2005 Nov 15.

Reference Type BACKGROUND
PMID: 16297506 (View on PubMed)

Theilla M, Schwartz B, Cohen J, Shapiro H, Anbar R, Singer P. Impact of a nutritional formula enriched in fish oil and micronutrients on pressure ulcers in critical care patients. Am J Crit Care. 2012 Jul;21(4):e102-9. doi: 10.4037/ajcc2012187.

Reference Type BACKGROUND
PMID: 22751375 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.ncbi.nlm.nih.gov/books/NBK65149/

Incidence of diabetic foot ulcer and lower extremity amputation among Medicare beneficiaries, 2006 to 2008: Data Points #2.

Other Identifiers

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1876718

Identifier Type: -

Identifier Source: org_study_id