Clinical trial NCT06676124: MMP-9/NGAL Modulation by Piper Crocatum in Early Diabetic Nephropathy
Official title: Modulation of MMP-9/NGAL Ratio in Diabetic Patients With Early Renal Dysfunction by Piper Crocatum Functional Foods
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Early Renal Dysfunction in Diabetes
Diabetic Nephropathy
Inflammation and Oxidative Stress in Diabetic Patients
Keywords: Early Renal Dysfunction
Diabetes Complications
Piper crocatum
Antioxidants
Anti-inflammatory
Renal Biomarkers
Functional Foods
Lead sponsor: Hasanuddin University
Sponsor class: OTHER
First posted: 2024-11-06
Enrollment: 387
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two parallel groups: one group receives Piper crocatum cookies, and the other group receives placebo cookies for 12 weeks
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to determine whether functional foods made with Piper crocatum (red betel leaf) can reduce kidney damage markers in people with diabetes who have early kidney dysfunction. Researchers aim to find out if these foods can help decrease inflammation and oxidative stress, which are known to worsen kidney problems in diabetes.

Participants are divided into two groups: one group will consume cookies containing Piper crocatum extract, while the other group will consume similar cookies without the extract (placebo). They will eat these cookies twice a day for 12 weeks.

This study will measure changes in two main kidney damage markers-MMP-9 and NGAL-before and after the intervention to see if Piper crocatum helps lower these markers and supports kidney health.

Detailed description: This clinical trial investigates the potential of Piper crocatum-based functional foods to modulate renal biomarkers in diabetic patients with early renal dysfunction. Diabetic nephropathy, a common and severe complication of diabetes, is largely driven by chronic inflammation and oxidative stress. These conditions exacerbate renal damage and increase the risk of end-stage renal disease (ESRD). Current therapeutic approaches often fail to address these underlying inflammatory and oxidative pathways adequately, creating a need for complementary or alternative interventions.

Study Design and Intervention This study is a double-blind, randomized, placebo-controlled trial conducted in Indonesia. A total of 387 diabetic participants with early signs of renal dysfunction were recruited, and participants were randomly assigned to one of two groups: an intervention group and a placebo group. The intervention group receives cookies containing standardized extracts of Piper crocatum, a plant known for its high antioxidant and anti-inflammatory content, particularly flavonoids and glycoside polyphenols. The placebo group receives cookies identical in taste and appearance but without the active Piper crocatum ingredients.

Participants in both groups are instructed to consume two cookies per day for 12 weeks. The active cookies are carefully formulated to maintain bioactive integrity during production, ensuring that the concentration of Piper crocatum's key compounds is consistent and effective. The formulation includes 10% of an ethyl acetate fraction of Piper crocatum extract, chosen for its high antioxidant activity.

Objectives and Hypotheses The primary objective of this trial is to assess whether the consumption of Piper crocatum cookies reduces levels of matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL) in diabetic patients with early renal dysfunction. MMP-9, an enzyme involved in extracellular matrix (ECM) remodeling, is a known marker for renal inflammation and fibrosis in diabetic nephropathy. NGAL, a marker of tubular injury, provides an indicator of oxidative stress and renal health. The secondary objective is to examine whether the MMP-9/NGAL ratio improves with Piper crocatum intervention, indicating a potential protective effect on both glomerular and tubular health.

Mechanism of Action and Prior Evidence The therapeutic action of Piper crocatum is hypothesized to involve the modulation of oxidative stress and inflammation through several key pathways. Flavonoids and glycoside polyphenols in Piper crocatum have demonstrated strong antioxidative properties, capable of scavenging free radicals and stabilizing cellular structures. These compounds also appear to influence regulatory proteins, including p53, SOD1, and E-cadherin, which play roles in cellular repair, apoptosis, and oxidative defense.

Recent studies have shown that Piper crocatum extracts can downregulate MMP-9 expression, thus preventing excessive ECM degradation and promoting tissue stability. Additionally, by reducing NGAL levels, Piper crocatum may protect against tubular injury, potentially lowering the risk of nephropathy progression. The current study expands on these findings by exploring Piper crocatum's effects specifically within a diabetic population with early renal dysfunction.

Biomarker Analysis Biomarker measurements for MMP-9 and NGAL will be conducted at baseline (Day 0) and after the 12-week intervention (Day 84). Blood samples will be collected following an 8-hour fasting period, and serum levels of MMP-9 and NGAL will be quantified using validated ELISA kits. These biomarker measurements provide a direct assessment of the intervention's impact on key pathways of renal injury and repair.

Statistical Methods The analysis will use both paired and independent statistical tests to compare biomarker levels between and within groups. The primary analysis will involve comparing the mean change in MMP-9, NGAL, and the MMP-9/NGAL ratio between the intervention and placebo groups. Effect sizes will be calculated to determine the magnitude of change associated with the Piper crocatum intervention. All statistical analyses will use a significance threshold of p \< 0.05.

Expected Outcomes and Clinical Implications The anticipated outcome is a significant reduction in MMP-9, NGAL, and the MMP-9/NGAL ratio in the intervention group compared to the placebo group, indicating a potential protective effect on renal health. If successful, this study could establish Piper crocatum-based functional foods as a novel adjunct therapy for diabetic nephropathy, offering a dietary approach to mitigate the progression of renal dysfunction in diabetic populations.

By providing insights into a natural, bioactive intervention, this study may open new avenues for integrating functional foods into diabetic care to improve outcomes and enhance quality of life for patients at risk of advanced renal complications.

Eligibility criteria: Inclusion Criteria:

* Adults aged over 20 years.
* Diagnosed with Diabetes Mellitus (DM).
* Serum urea levels above 43 mg/dL or serum creatinine levels above 0.90 mg/dL.

Exclusion Criteria:

* Pregnant or breastfeeding individuals.
* Patients with other medical conditions that require intensive care.
* Patients currently undergoing therapy for hypoalbuminemia.
* Known allergies to any ingredients in the study cookies.
* Other chronic conditions that might interfere with the study protocol (e.g., severe cardiovascular disease).

Primary outcomes:
measure: Change in MMP-9 and NGAL Levels in Diabetic Patients with Early Renal Dysfunction
timeFrame: Baseline and 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Makassar
country: Indonesia
facility: Public Health Center in Makassar, Indonesia
state: South Sulawesi
Study officials:
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