Effect of Golden Rice-Piper Crocatum Cookies on Neuropathy Prevention in Diabetes

NCT07272993 | Active Not Recruiting

• 1 other identifier: UH2508103
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes mellitus is a chronic disease that can cause many complications, one of the most common being diabetic neuropathy. This condition occurs due to long-term high blood sugar levels that damage the nerves. Symptoms include tingling, burning, pain, and loss of sensation in the feet. If not prevented, neuropathy can progress to diabetic foot ulcers and even lead to amputation. This study aims to evaluate whether Golden Rice Cookies enriched with Red Betel Leaf (Piper crocatum) can help prevent diabetic neuropathy in patients with diabetes. Golden rice is a type of rice that contains beta-carotene (provitamin A) and high fiber, which help maintain stable blood sugar levels and reduce oxidative stress. Meanwhile, red betel leaf contains flavonoids, polyphenols, and alkaloids with antioxidant, anti-inflammatory, and hypoglycemic properties that may protect nerves from damage. Cookies were chosen as the intervention form because they are practical, easy to consume, and widely accepted by patients. In this study, patients will be divided into two groups: an intervention group receiving golden rice cookies with red betel leaf extract, and a control group receiving golden rice cookies without the extract. Changes in neuropathy symptoms will be assessed using the Neuropathy Symptom Score (NSS) before and after the intervention. The expected outcome of this research is to provide scientific evidence that the combination of golden rice and red betel leaf in the form of cookies can serve as an effective, safe, and acceptable functional food to help prevent diabetic neuropathy. This nutritional intervention may support comprehensive diabetes management and improve patients' quality of life.

Conditions

Diabetic Neuropathy; Diabetes Mellitus (DM); Functional Food; Nutritional Intervention; Blood Glucose

Outcome Measures

Primary Outcomes (1)

• Change in Neuropathy Symptoms Score (NSS)

  Neuropathy Symptoms Score (NSS) is a standardized questionnaire used to assess the severity of peripheral neuropathy symptoms in patients with diabetes. The instrument evaluates common neuropathic symptoms including numbness, burning sensation, tingling, cramps, and pain. Each symptom is scored based on presence and characteristics (e.g., location, timing, aggravating factors), with a total score ranging from 0 to 9, where higher scores indicate more severe neuropathic symptoms. Assessment is conducted through participant interview by trained clinical assessors

  Baseline (Day 0) to Day 28

Secondary Outcomes (2)

• Fasting Blood Glucose Level

  Baseline Day 0, Day 14, and Day 28

• Change in Peripheral Sensation Via Monofilament Test

  Baseline (Day 0) and Post intervention (Day 28)

Other Outcomes (1)

• Adherence to Cookie Consumption

  Daily from Day 1 to Day 28

Study Arms (2)

Golden Rice Cookies Enriched with Piper Crocatum

EXPERIMENTAL

Participants assigned to this arm will receive cookies formulated with golden rice flour and enriched with Piper crocatum (red betel leaf extract). The cookies are consumed daily over a 28-day period. This intervention is designed to evaluate the potential neuroprotective effects of Piper crocatum in preventing or reducing symptoms of diabetic neuropathy among patients with type 2 diabetes mellitus. The formulation aims to leverage the antioxidant and anti-inflammatory properties of Piper crocatum in combination with the nutritional benefits of golden rice

Dietary Supplement: Golden Rice Cookies With Piper Crocatum

Golden Rice Cookies Without Piper Crocatum

ACTIVE COMPARATOR

Participants in this arm will receive cookies made exclusively from golden rice flour, without the addition of Piper crocatum. These cookies are also consumed daily for 28 days. This control intervention is intended to isolate the effect of Piper crocatum by comparing outcomes with the experimental group. Both cookie types are matched in appearance, taste, and packaging to maintain blinding integrity.

Dietary Supplement: Golden Rice Cookies Without Piper Crocatum

Interventions

Golden Rice Cookies With Piper Crocatum DIETARY_SUPPLEMENT

This intervention consists of a functional food product in the form of cookies made from golden rice flour, enriched with Piper crocatum (red betel leaf extract). The cookies are administered orally, once daily, over a 28-day period. What distinguishes this intervention from others is the combination of golden rice a biofortified grain rich in beta-carotene with Piper crocatum, a traditional Indonesian medicinal plant known for its antioxidant and anti-inflammatory properties. The formulation is designed to target diabetic neuropathy prevention by enhancing neuroprotective effects through dietary supplementation. The product is standardized in dosage, appearance, and packaging to support double-blind administration and ensure consistency across participants.

Golden Rice Cookies Enriched with Piper Crocatum

Golden Rice Cookies Without Piper Crocatum DIETARY_SUPPLEMENT

This intervention consists of cookies made from golden rice flour without the addition of Piper crocatum (red betel leaf extract). The cookies are administered orally, once daily, for 28 consecutive days. Although lacking the herbal component, golden rice itself is a biofortified grain rich in beta-carotene, offering nutritional value. The control product is matched in appearance, taste, and packaging to the experimental cookies to maintain double-blind conditions. This intervention serves as an active comparator to isolate the effect of Piper crocatum in preventing diabetic neuropathy symptoms

Golden Rice Cookies Without Piper Crocatum

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults aged between 18 and 59 years
• Diagnosed with diabetes mellitus based on medical records
• Able to read and communicate effectively
• Willing to participate in the study, sign the informed consent form, and commit to consuming the cookies according to the prescribed dosage

You may not qualify if:

• Pregnant or breastfeeding women
• Patients with a history of allergy to any component of the intervention, including golden rice or Piper crocatum
• Patients with active diabetic foot ulcers

Sponsors & Collaborators

• Hasanuddin University: lead

Study Sites (1)

UPTD Puskesmas Lompeta Singgani Tambu

Donggala, Central Sulawesi, 94355, Indonesia

Location

Related Publications (3)

• Setyawati A, Saleh A, Tahir T, Yusuf S, Syahrul S, Aminuddin A, Raihan M, Jafar N, Hamzah H, Arfian N. 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. JMIR Res Protoc. 2024 Feb 29;13:e49940. doi: 10.2196/49940.

  PMID: 38422498 BACKGROUND

• Dyck PJ, Kratz KM, Karnes JL, et al. The Neuropathy Symptom Score: A systematic measure for evaluation of distal symmetric polyneuropathy in clinical research. Neurology. 1997;48(3):593-601.

  RESULT

• Setyawati A, Wahyuningsih MSH, Nugrahaningsih DAA, Effendy C, Fneish F, Fortwengel G. Piper crocatum Ruiz & Pav. ameliorates wound healing through p53, E-cadherin and SOD1 pathways on wounded hyperglycemia fibroblasts. Saudi J Biol Sci. 2021 Dec;28(12):7257-7268. doi: 10.1016/j.sjbs.2021.08.039. Epub 2021 Aug 19.

  PMID: 34867030 RESULT

Related Links

• Official Website of The Faculcy of Nursing, Hasanuddin University
• Hasanuddin University Official Website

MeSH Terms

Conditions

Diabetic Neuropathies; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Dr. Andina Setyawati, S.Kep.,Ns.,M.Kep

  Faculty of Nursing, Hasanuddin University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: In this study, participants will not be informed whether they are receiving golden rice cookies with Piper crocatum extract or golden rice cookies without Piper crocatum. The cookies are prepared to be similar in appearance, texture, and packaging to minimize bias. Outcome assessors who evaluate neuropathy symptoms using the Neuropathy Symptom Score (NSS) and perform the monofilament test will also be masked to group assignment. This masking strategy is intended to reduce reporting bias from participants and measurement bias from outcome assessors, ensuring the reliability of the study results.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: S.Kep.,Ns

Model Details: This study is designed as a randomized controlled trial using a pre-test and post-test design with a control group. Eligible participants are patients diagnosed with diabetes mellitus who present with symptoms of diabetic neuropathy. Participants will be randomly assigned into two groups: the intervention group receiving golden rice cookies enriched with Piper crocatum extract, and the control group receiving golden rice cookies without Piper crocatum. The intervention will be administered for 28 consecutive days, with both groups monitored under similar conditions. Assessments will be conducted at baseline (pre-test) and after the intervention period (post-test). The primary outcome measure is the change in Neuropathy Symptom Score (NSS), while secondary outcomes include blood glucose monitoring and simple neuropathy screening tests (monofilament test). This interventional model allows for direct comparison between the functional food intervention and the control to determine the ef

Study Record Dates

• First Submitted: September 30, 2025
• First Posted: December 9, 2025
• Study Start: October 20, 2025
• Primary Completion: November 30, 2025
• Study Completion: December 31, 2025
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)