Nutritional Supplement on Wound Healing in Diabetic Foot

Clinical Effectiveness and Molecular Mechanisms of Nutritional Supplement on Wound Healing in Diabetic Patients With Limb-threatening Foot Ulcer

Diabetic foot ulcer (DFU) is the leading cause of non-traumatic limb loss in adult worldwide. One of the major causes of limb loss in patients with DFU is poor wound healing. It is known that nutrition plays a key role in wound healing, not only because of the required calories, but more importantly for collagen remodeling by specific amino acids (arginine, glutamine, and β-hydroxy-β-methylbutyrate).

Nevertheless, few studies have investigated nutritional supplements in patients with poor wound healing of DFU. Difficulties in assessing the severity of a wound and poor adherence to drug and food supplements at home may be important factors for the negative results shown in a most recent prospective randomized controlled trial. The diabetic foot center in Chang Gung Memorial hospital has extensive experience in caring for patients with limb-threatening DFU and we recently reported that poor nutritional status in our patients correlated to poor treatment outcomes. The aim of this study is to evaluate the clinical efficacy and possible molecular mechanisms in nutritional treatment for limb-threatening DFU. A total of 70 patients will be enrolled and randomized into study and control groups. All subjects will receive standard care. Additional amino acid supplements containing arginine, glutamine, and β-hydroxy-β-methylbutyrate or a control (high protein formula powder) will be given orally twice a day for 21 days, and the percentage change in wound size will then be measured. Complete healing time, recurrence or major adverse cardiac events will be recorded during one year of follow up. Data on wound size, nutritional status, and levels of matrix metallopeptidase (MMP)-2, MMP-9, nutrient molecules (measured by ABSOLUTE/DQ P180 KIT (LC MS/MS) will be recorded before and after the nutritional supplementation. In addition, the pioneer factor forkhead box protein A2 (FOXA2) that binds native chromatin and bookmarks genomic regions for transcriptional activity may play a role in nutritional supplements in acute stressed diabetic patients. Therefore, we intend to conduct a pilot study on the for FOXA2 gene in maintaining glucose homeostasis in diabetic foot patients after nutritional interventions.

Study Overview

• Status: Unknown
• Conditions: Diabetic Foot
• Intervention / Treatment: Dietary supplement: Abound

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yu-Yao Huang, MD, PhD; Phone Number: 8826 +886-3-3281200; Email: yyh@cgmh.org.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Yu-Yao Huang; Phone Number: 8826 +88633281200; Email: yyh@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects will be considered for entry if they are men or non-pregnant women, aged ≥ 40 years or ≤ 80 years
2. a serum albumin level between 2.0 mg/dL and 4.0 mg/dL, had peripheral occlusive arterial disease with an ankle-brachial index (ABI) ≤0.9 or Doppler arterial waveforms that are biphasic or monophasic
3. a serum C-reactive protein level ≤ 50 mg/L .

Exclusion Criteria:

Subjects will be excluded from the study if they have serious comorbidities such as

1. pneumonia,
2. active malignancy, severe renal function impairment (creatinine < 3 mg/dl), heart failure (NYHA Fc ≥ 3),
3. liver failure/cirrhosis (Child class B or C),
4. myocardial infarction in the past 3 months,
5. wounds complicated with persistent osteomyelitis,
6. a Charcot deformity,
7. alcohol/substance abuse,
8. any mental or physiological condition that may interfere with dietary intake,
9. history of allergy to any of the ingredients in the supplement,
10. those who are unable to follow orders or cooperate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abound supplement; The participant will take the supplementation drink containing 79 kcal, 7 g L-arginine, 7 g L-glutamine and 1.5 g calcium β-hydroxy-β-methylbutyrate (Abound; Abbott Nutrition, Columbus, OH, USA). The subjects will be instructed to drink the entire packet dissolved in 250 ml of water twice per day for 21 days.	Dietary supplement: Abound; Study Group will take the supplementation drink containing 79 kcal, 7 g L-arginine, 7 g L-glutamine and 1.5 g calcium β-hydroxy-β-methylbutyrate (Abound; Abbott Nutrition, Columbus, OH, USA). The subjects will be instructed to drink the entire packet dissolved in 250 ml of water twice per day for 21 days.
No Intervention: Traditional supplement; The participant will take traditional diabetes-specific formula as provided by dietitians.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PEDIS score	Measurement of wound size change	one year

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2018
• Primary Completion (Anticipated): May 15, 2020
• Study Completion (Anticipated): May 15, 2020

Study Registration Dates

• First Submitted: September 11, 2018
• First Submitted That Met QC Criteria: September 18, 2018
• First Posted (Actual): September 20, 2018

Study Record Updates

• Last Update Posted (Actual): September 20, 2018
• Last Update Submitted That Met QC Criteria: September 18, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Ulcer; Diabetic Foot
• Other Study ID Numbers: 104-9965A3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No