Immunonutrition for Diabetic Foot Ulcers

NCT05281562 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 1876718
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus; Diabetic Peripheral Neuropathy; Diabetic Foot Ulcer

Outcome Measures

Primary Outcomes (2)

• 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 6 weeks for both the standard of care group and experimental group and calculate the change in ulcer scores from consent to 6 weeks.

  6 weeks

• 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 6 weeks.

  6 weeks

Secondary Outcomes (2)

• Effect of Supplemental Immunonutrition on Patient Satisfaction in Patients With Diabetic Foot Ulcers.

  6 weeks

• 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.

  1 year

Study Arms (2)

Standard of Care Group

NO INTERVENTION

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

Immunonutrition Supplementation Group

EXPERIMENTAL

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.

Drug: Lovaza; Drug: L-Arginine Powder; Drug: Vitamin C

Interventions

Lovaza DRUG

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

Also known as: omega-3 fatty acids, omega-3-acid ethyl esters

Immunonutrition Supplementation Group

L-Arginine Powder DRUG

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

Also known as: Arginine, 2-amino-5-guanidinopentanoic acid

Immunonutrition Supplementation Group

Vitamin C DRUG

Daily dose of 500 mg Vitamin C, powder form.

Also known as: Ascorbic acid

Immunonutrition Supplementation Group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prisma Health-Midlands: lead

Study Sites (1)

Prisma Health

Columbia, South Carolina, 29203, United States

Location

Related Publications (13)

• 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.

  PMID: 18801858 BACKGROUND

• 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.

  PMID: 28657897 BACKGROUND

• 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.

  PMID: 24018732 BACKGROUND

• 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.

  PMID: 31456118 BACKGROUND

• 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.

  PMID: 24186882 BACKGROUND

• 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.

  PMID: 24347529 BACKGROUND

• 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.

  PMID: 25371851 BACKGROUND

• 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.

  PMID: 18316142 BACKGROUND

• 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.

  PMID: 21664268 BACKGROUND

• 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.

  PMID: 25643304 BACKGROUND

• 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.

  PMID: 22399084 BACKGROUND

• 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.

  PMID: 16297506 BACKGROUND

• 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.

  PMID: 22751375 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus; Diabetic Foot

Interventions

Omacor; Fatty Acids, Omega-3; Arginine; Ascorbic Acid

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetic Neuropathies

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: J. Benjamin Jackson
• Organization: Prisma Health

benjamin.jackson@prismahealth.org

803-296-9610

Study Officials

• J. Benjamin Jackson, MD

  Prisma Health-Midlands

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 16, 2022
• Study Start: February 8, 2023
• Primary Completion: March 20, 2023
• Study Completion: March 20, 2023
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)