Efficacy of Hyaluronic Acid Cream in Preventing Foot Ulceration Risk in Patients With Type 2 Diabetes and Moderate-to-Severe Peripheral Neuropathy: A Randomized Clinical Trial.

NCT07131410 | Enrolling By Invitation DMC

• 1 other identifier: Universidad Miguel Hernández
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

A triple-blind randomized clinical trial aimed at evaluating the efficacy of a hyaluronic acid cream in preventing foot ulcers in patients with type 2 diabetes and moderate-to-severe peripheral neuropathy. The primary objective is to determine the effectiveness of this cream in preventing ulcerations after 12 months of use in this population, compared to the use of another cream containing 10% urea. Secondary objectives include assessing changes in hydration, skin stiffness, and pH across various areas of the foot, with results compared between the intervention and control groups. The study will be conducted at Miguel Hernández University between 2025 and 2027. A total of 166 adult participants with type 2 diabetes and moderate-to-severe peripheral neuropathy will be randomized into two groups: the intervention group, which will apply the hyaluronic acid cream daily, and the control group, which will use a 10% urea cream. Measurements of skin hydration, pH, and stiffness, along with the xerosis index, will be taken during three scheduled visits (at 3, 6, and 12 months). Neuropathy will be assessed through sensitivity and reflex tests, while sociodemographic and clinical variables will be recorded at the start of the study. Participants will log their treatment adherence and any potential adverse effects through a mobile application. The data obtained on skin hydration, pH, and stiffness will be analyzed to identify differences between the two groups, with differences considered statistically significant if p \< 0.05. This study aims to provide evidence on the effectiveness of hyaluronic acid in preventing ulcerations and improving skin characteristics of the foot in patients with diabetes and peripheral neuropathy.

Conditions

DIABETES

Keywords

WOUND; DIABETIC FOOT

Outcome Measures

Primary Outcomes (1)

• Photo analysis

  The occurrence of dermal lesions on the skin will be recorded, specifying their location, type, and size. The patient will be able to report any dermal lesion to the investigator via the app, and the lesion will be assessed at the university clinic, regardless of the study's scheduled follow-up visit

  12 months

Study Arms (2)

Patients who apply 10% urea daily

SHAM COMPARATOR

Participants will apply a 10% urea cream following the same protocol. Patients will receive the container cream for application on both feet after thoroughly washing and drying them. It is recommended to use an amount the size of a hazelnut for each foot, spreading it in a thin layer over the entire foot, excluding the interdigital area. The application will be done every night for twelve months. The product will be massaged into the foot for 15 seconds. During the study, participants will not be allowed to use any other topical product (cream, emulsion, gel, lotion, or oil) on their feet and/or nails.

Other: Group hialuronyc

Patients who apply hyaluronic acid daily

EXPERIMENTAL

Patients will receive the container with Hialucic® cream for application on both feet after thoroughly washing and drying them. It is recommended to use an amount the size of a hazelnut for each foot, spreading it in a thin layer over the entire foot, excluding the interdigital area. The application will be done every night for twelve months. The product will be massaged into the foot for 15 seconds. During the study, participants will not be allowed to use any other topical product (cream, emulsion, gel, lotion, or oil) on their feet and/or nails.

Other: Group hialuronyc

Interventions

Group hialuronyc OTHER

Patients will receive the container with cream for application on both feet after thoroughly washing and drying them. It is recommended to use an amount the size of a hazelnut for each foot, spreading it in a thin layer over the entire foot, excluding the interdigital area. The application will be done every night for twelve months. The product will be massaged into the foot for 15 seconds. During the study, participants will not be allowed to use any other topical product (cream, emulsion, gel, lotion, or oil) on their feet and/or nails.

Patients who apply 10% urea daily; Patients who apply hyaluronic acid daily

Eligibility Criteria

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

You may qualify if:

• Adults aged 18 or older, diagnosed with type 2 diabetes and moderate-to-severe peripheral neuropathy (diagnosed with a score ≥6 on the Michigan scale), who have not used any topical moisturizer or keratolytic agents on their feet for at least two weeks prior

You may not qualify if:

• Presence of ulcerative skin lesions on the foot Diagnosed peripheral arterial disease, indicated by the absence of both peripheral pulses and/or Ankle-Brachial Index less than 1 or greater than 1.4 Dermatological diseases affecting foot hydration: atopic dermatitis, ichthyosis, or psoriasis Use of custom-made plantar orthoses, as the material could affect foot hydration

Sponsors & Collaborators

• University of Malaga: lead

Study Sites (1)

University of Malaga

Málaga, 29071, Spain

Location

Related Publications (6)

• Fitzner A, Knuhr K, Brandt M, Bielfeldt S. Investigating the effect of the pH of foot care product formulations on pedal skin in diabetic and non-diabetic subjects. Int J Cosmet Sci. 2023 Aug;45(4):524-538. doi: 10.1111/ics.12861. Epub 2023 Apr 27.

  PMID: 37014141 RESULT

• Garrigue E, Martini J, Cousty-Pech F, Rouquier A, Degouy A. Evaluation of the moisturizer Pedimed((R)) in the foot care of diabetic patients. Diabetes Metab. 2011 Sep;37(4):330-5. doi: 10.1016/j.diabet.2010.12.004. Epub 2011 Feb 23.

  PMID: 21349756 RESULT

• Federici A, Federici G, Milani M. An urea, arginine and carnosine based cream (Ureadin Rx Db ISDIN) shows greater efficacy in the treatment of severe xerosis of the feet in Type 2 diabetic patients in comparison with glycerol-based emollient cream. A randomized, assessor-blinded, controlled trial. BMC Dermatol. 2012 Sep 25;12:16. doi: 10.1186/1471-5945-12-16.

  PMID: 23009311 RESULT

• Cristaudo A, Francesconi L, Ambrifi M, Frasca M, Cavallotti C, Sperduti E. Efficacy of an emollient dermoprotective cream in the treatment of elderly skin affected by xerosis. G Ital Dermatol Venereol. 2015 Jun;150(3):297-302.

  PMID: 25946673 RESULT

• Couteau C, Coiffard LJ, Sebille-Rivain V. Influence of excipients on moisturizing effect of urea. Drug Dev Ind Pharm. 2006 Feb;32(2):239-42. doi: 10.1080/03639040500466361.

  PMID: 16537204 RESULT

• Chicharro-Luna E, Zunica-Garcia S, Martinez-Algarra C, Gracia-Sanchez A. Age-related variations in stratum corneum hydration in the foot. Maturitas. 2024 Nov;189:108104. doi: 10.1016/j.maturitas.2024.108104. Epub 2024 Aug 22.

  PMID: 39180901 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Wounds and Injuries; Diabetic Foot

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Efficacy of Hyaluronic Acid Cream in Preventing Foot Ulceration Risk in Patients with Type 2 Diabetes and Moderate-to-Severe Peripheral Neuropathy: A Randomized Clinical Trial.

Study Record Dates

• First Submitted: November 9, 2024
• First Posted: August 20, 2025
• Study Start: February 15, 2024
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): March 15, 2027
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)