Matrix Metalloproteinase-9 Testing of Golden Rice Cookies With Piper Crocatum Active Extract for Preventing Foot Ulcers in Patients With Diabetes: Protocol for a Randomized Controlled Trial (Preprint)

Abstract

Diabetic foot ulcers (DFUs) present a formidable challenge to both patients and health care systems. DFUs significantly reduce the quality of life for patients, prolong hospital stays, and are the cause of approximately 70,000 lower limb amputations across the globe annually. Prevention of DFUs primarily involves the optimization of blood sugar levels and the effective management of complications, particularly peripheral neuropathy. Golden Rice has been proven to lower blood sugar levels due to its beta-carotene content, and Piper crocatum (<i>P. crocatum</i>) has been found to be effective in reducing the risk factors of DFUs through biomolecular regulation because of its polyphenol content.

The principal objective of this study is to identify the efficacy of <i>P. crocatum</i>–enriched cookies, with Golden Rice as their primary ingredient, in preventing DFUs. The evaluation will center on their impact on the expression of matrix metalloproteinase-9 (MMP-9), a pivotal factor in the development of DFUs.

This study is an experimental clinical research that follows the randomized controlled trial method and uses a single-blind design. The participants in the study are outpatients from primary health centers in Makassar, Indonesia, who have been diagnosed with diabetes mellitus. The sample for the study will be randomly selected and subsequently categorized into 2 groups: the intervention group and the control group. The intervention group consumes <i>P. crocatum</i>–enriched Golden Rice cookies, while the control group receives cookies without these additives. The participants from both groups will consume their respective cookies (packaged identically) twice a day for 14 days. The cookies will be prepared according to a modified recipe with an emphasis on low glucose content, resulting in 51 calories per cookie, comprising 1% carbohydrates, 6% fat, 4% cholesterol, and 4% fiber, excluding gluten, sugar, and salt. They will be baked at 158°C for 20 minutes. The process involves the addition of 20% Golden Rice and 10% <i>P. crocatum</i> ethanol extract, both prepared via maceration with 96% ethanol. The dependent variable in this study is the expression of gelatinases matrix metalloproteinase, to be assessed at 2 distinct time points—preintervention (pretest) and postintervention (posttest)—with the evaluation conducted through the western blotting method.

The recruitment and testing phase started in January 2024. The study is scheduled to be completed by the end of March 2024. Data analysis will commence in April 2024, and the publication of the results is anticipated in the same year (2024). The study will report on the changes in primary data, encompassing gelatinases matrix metalloproteinase, as well as secondary data, including the ankle-brachial index, neuropathy score, and random blood glucose level.

The findings of this trial are expected to significantly impact the selection of strategies by health care practitioners to enhance diabetes self-management, particularly in the domain of therapeutic snacking, for patients diagnosed with diabetes mellitus.

Thai Clinical Trials Registry TCTR20230502001; https://www.thaiclinicaltrials.org/show/TCTR20230502001

PRR1-10.2196/49940