Early Renal Dysfunction in DiabetesMMP-9/NGALNCT06676124
MMP-9/NGAL Modulation by Piper Crocatum in Early Diabetic Nephropathy
A study testing Piper crocatum Extract Cookie in people with Early Renal Dysfunction in Diabetes and Diabetic Nephropathy, run by Hasanuddin University at 1 site in Indonesia.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Early Renal Dysfunction in Diabetes, Diabetic Nephropathy, Inflammation and Oxidative Stress in Diabetic Patients
- What is being tested?
- Piper crocatum Extract Cookie
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 387 participants
- Where
- 1 siteIndonesia
- Study dates
- 15 Jun 2024to 16 Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
Indonesia1 site
Public Health Center in Makassar, Indonesia
Makassar, South Sulawesi, 90245
About this study
Official title: Modulation of MMP-9/NGAL Ratio in Diabetic Patients With Early Renal Dysfunction by Piper Crocatum Functional Foods
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.
Read the 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.
- Conditions
- Early Renal Dysfunction in Diabetes, Diabetic Nephropathy, Inflammation and Oxidative Stress in Diabetic Patients
- Being tested
- Piper crocatum Extract Cookie, Placebo Comparator
- Keywords
- Early Renal Dysfunction, Diabetes Complications, Piper crocatum, Antioxidants, Anti-inflammatory, Renal Biomarkers, Functional Foods
- Medical subject headings
- Diabetic Nephropathies, Inflammation, Renal Insufficiency, Diabetes Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piper crocatum Extract CookieDietary supplement
Participants in the intervention group will receive cookies containing a standardized 10% ethyl acetate extract of Piper crocatum, known for its antioxidant and anti-inflammatory properties. These cookies will be consumed twice daily for 12 weeks. The intervention aims to assess the effects of Piper crocatum on renal biomarkers, such as MMP-9 and NGAL, in diabetic patients with early renal dysfunction
Placebo ComparatorDietary supplement
Participants in the placebo group will receive cookies that are identical in appearance, taste, and texture to the active Piper crocatum cookies but do not contain the Piper crocatum extract. These cookies will be consumed twice daily for 12 weeks, serving as a control to assess the effects of the active intervention on renal biomarkers associated with diabetic nephropathy.
| Study group | Role | What they receive |
|---|---|---|
| Piper crocatum Cookie Group | Experimental | Participants in this group will receive bioactive-rich cookies containing Piper crocatum extract, known for its antioxidant and anti-inflammatory properties. They will consume two cookies daily for 12 weeks, each formulated with a standardized 10% concentration of the ethyl acetate fraction of Piper crocatum extract. The intervention aims to modulate renal biomarkers associated with diabetic nephropathy Receives: Dietary Supplement: Piper crocatum Extract Cookie |
| Placebo Cookie Group | Placebo comparator | Participants in this group will receive placebo cookies that are identical in appearance, taste, and texture to the Piper crocatum cookies but do not contain the active Piper crocatum extract. They will consume two cookies daily for 12 weeks. This group serves as a comparison to evaluate the effects of the Piper crocatum extract in the intervention group Receives: Dietary Supplement: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in MMP-9 and NGAL Levels in Diabetic Patients with Early Renal Dysfunction
This measure evaluates the change in serum levels of matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL) in diabetic patients with early renal dysfunction after 12 weeks of intervention. MMP-9 is associated with renal inflammation and extracellular matrix remodeling, while NGAL is a marker of tubular injury and oxidative stress. Blood samples will be collected at baseline and at the end of the 12-week period, and serum levels of MMP-9 and NGAL will be quantified using validated ELISA kits. This assessment aims to determine the potential effects of the Piper crocatum intervention on renal health by observing significant changes in these biomarkers
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2024
- Study start15 Jun 2024
- Primary completion5 Sep 2024
- Study completion16 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Early Renal Dysfunction in DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two parallel groups: one group receives Piper crocatum cookies, and the other group receives placebo cookies for 12 weeks
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 387 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hasanuddin University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andina Setyawati, Hasanuddin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06676124
- Sponsor's protocol ID
- PROT-2024-UH
- Other IDs
- 1220/UN4.14.1/TP.01.02/2024
- Acronym
- MMP-9/NGAL
- Status last verified
- Nov 2024
- First submitted
- 4 Nov 2024
- Last updated
- 6 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be routinely shared to protect participant privacy and confidentiality. However, data may be made available to qualified researchers upon request, subject to approval by the study's principal investigator and in compliance with relevant privacy regulations and institutional policies.
Publications
Serra R, Grande R, Butrico L, Buffone G, Calio FG, Squillace A, Rizzo BA, Massara M, Spinelli F, Ferrarese AG, de Caridi G, Gallelli L, de Franciscis S. Effects of a new nutraceutical substance on clinical and molecular parameters in patients with chronic venous ulceration. Int Wound J. 2016 Feb;13(1):88-96. doi: 10.1111/iwj.12240. Epub 2014 Feb 25.
PubMed 24612734Rojas-Quintero J, Wang X, Tipper J, Burkett PR, Zuniga J, Ashtekar AR, Polverino F, Rout A, Yambayev I, Hernandez C, Jimenez L, Ramirez G, Harrod KS, Owen CA. Matrix metalloproteinase-9 deficiency protects mice from severe influenza A viral infection. JCI Insight. 2018 Dec 20;3(24):e99022. doi: 10.1172/jci.insight.99022.
PubMed 30568032Rodriguez-Sanchez E, Navarro-Garcia JA, Aceves-Ripoll J, Abarca-Zabalia J, Susmozas-Sanchez A, Bada-Bosch T, Hernandez E, Merida-Herrero E, Andres A, Praga M, Fernandez-Ruiz M, Aguado JM, Segura J, Ruilope LM, Ruiz-Hurtado G. Variations in Circulating Active MMP-9 Levels During Renal Replacement Therapy. Biomolecules. 2020 Mar 26;10(4):505. doi: 10.3390/biom10040505.
PubMed 32225016Latronico T, Petraglia T, Sileo C, Bilancia D, Rossano R, Liuzzi GM. Inhibition of MMP-2 and MMP-9 by Dietary Antioxidants in THP-1 Macrophages and Sera from Patients with Breast Cancer. Molecules. 2024 Apr 10;29(8):1718. doi: 10.3390/molecules29081718.
PubMed 38675538Kumar M, Dev S, Khalid MU, Siddenthi SM, Noman M, John C, Akubuiro C, Haider A, Rani R, Kashif M, Varrassi G, Khatri M, Kumar S, Mohamad T. The Bidirectional Link Between Diabetes and Kidney Disease: Mechanisms and Management. Cureus. 2023 Sep 20;15(9):e45615. doi: 10.7759/cureus.45615. eCollection 2023 Sep.
PubMed 37868469Jones JI, Nguyen TT, Peng Z, Chang M. Targeting MMP-9 in Diabetic Foot Ulcers. Pharmaceuticals (Basel). 2019 May 22;12(2):79. doi: 10.3390/ph12020079.
PubMed 31121851Setyawati 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.
PubMed 34867030Setyawati 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.
PubMed 38422498Papadopoulou-Marketou N, Whiss PA, Eriksson AC, Hyllienmark L, Papassotiriou I, Wahlberg J. Plasma levels of tissue inhibitor of metalloproteinase-1 in patients with type 1 diabetes mellitus associate with early diabetic neuropathy and nephropathy. Diab Vasc Dis Res. 2021 Mar-Apr;18(2):14791641211002470. doi: 10.1177/14791641211002470.
PubMed 33775157Pan SC, Li CY, Kuo CY, Kuo YZ, Fang WY, Huang YH, Hsieh TC, Kao HY, Kuo Y, Kang YR, Tsai WC, Tsai ST, Wu LW. The p53-S100A2 Positive Feedback Loop Negatively Regulates Epithelialization in Cutaneous Wound Healing. Sci Rep. 2018 Apr 3;8(1):5458. doi: 10.1038/s41598-018-23697-5.
PubMed 29615682Nevo A, Armaly Z, Abd El Kadir A, Douvdevani A, Tovbin D. Elevated Neutrophil Gelatinase Lipocalin Levels Are Associated With Increased Oxidative Stress in Hemodialysis Patients. J Clin Med Res. 2018 Jun;10(6):461-465. doi: 10.14740/jocmr3360w. Epub 2018 Apr 13.
PubMed 29707087Danquah M, Owiredu WKBA, Jnr BAE, Serwaa D, Odame Anto E, Peprah MO, Obirikorang C, Fondjo LA. Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for detection of renal failure in hypertensives: a case-control study in a regional hospital in Ghana. BMC Nephrol. 2023 Apr 26;24(1):114. doi: 10.1186/s12882-023-03120-6.
PubMed 37101162Bae MJ, Karadeniz F, Oh JH, Yu GH, Jang MS, Nam KH, Seo Y, Kong CS. MMP-Inhibitory Effects of Flavonoid Glycosides from Edible Medicinal Halophyte Limonium tetragonum. Evid Based Complement Alternat Med. 2017;2017:6750274. doi: 10.1155/2017/6750274. Epub 2017 Sep 20.
PubMed 29234420Alsawaf S, Alnuaimi F, Afzal S, Thomas RM, Chelakkot AL, Ramadan WS, Hodeify R, Matar R, Merheb M, Siddiqui SS, Vazhappilly CG. Plant Flavonoids on Oxidative Stress-Mediated Kidney Inflammation. Biology (Basel). 2022 Nov 26;11(12):1717. doi: 10.3390/biology11121717.
PubMed 36552226Kunadu AP, Aboagye EF, Colecraft EK, Otoo GE, Adjei MYB, Acquaah E, Afrifa-Anane E, Amissah JGN. Low Consumption of Indigenous Fresh Dairy Products in Ghana Attributed to Poor Hygienic Quality. J Food Prot. 2019 Feb;82(2):276-286. doi: 10.4315/0362-028X.JFP-18-146.
PubMed 30682266
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of MMP-9/NGAL Ratio in Diabetic Patients With Early Renal Dysfunction by Piper Crocatum Functional Foods
- ClinicalTrials.gov ID
- NCT06676124
- Acronym / sponsor ID
- MMP-9/NGAL / PROT-2024-UH
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 387 participants (actual)
- Lead sponsor
- Hasanuddin UniversityUniversity, hospital or other
- Study start
- 15 Jun 2024 (actual)
- Primary completion
- 5 Sep 2024 (actual)
- Study completion
- 16 Sep 2024 (actual)
- First posted
- 6 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two parallel groups: one group receives Piper crocatum cookies, and the other group receives placebo cookies for 12 weeks
| Arm | Type | Receives |
|---|---|---|
| Piper crocatum Cookie Group | Experimental | Dietary Supplement: Piper crocatum Extract CookieParticipants in this group will receive bioactive-rich cookies containing Piper crocatum extract, known for its antioxidant and anti-inflammatory properties. They will consume two cookies daily for 12 weeks, each formulated with a standardized 10% concentration of the ethyl acetate fraction of Piper crocatum extract. The intervention aims to modulate renal biomarkers associated with diabetic nephropathy |
| Placebo Cookie Group | Placebo comparator | Dietary Supplement: Placebo ComparatorParticipants in this group will receive placebo cookies that are identical in appearance, taste, and texture to the Piper crocatum cookies but do not contain the active Piper crocatum extract. They will consume two cookies daily for 12 weeks. This group serves as a comparison to evaluate the effects of the Piper crocatum extract in the intervention group |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Piper crocatum Extract CookieParticipants in the intervention group will receive cookies containing a standardized 10% ethyl acetate extract of Piper crocatum, known for its antioxidant and anti-inflammatory properties. These cookies will be consumed twice daily for 12 weeks. The intervention aims to assess the effects of Piper crocatum on renal biomarkers, such as MMP-9 and NGAL, in diabetic patients with early renal dysfunction | Dietary supplement | Piper crocatum Cookie Group |
| Placebo ComparatorParticipants in the placebo group will receive cookies that are identical in appearance, taste, and texture to the active Piper crocatum cookies but do not contain the Piper crocatum extract. These cookies will be consumed twice daily for 12 weeks, serving as a control to assess the effects of the active intervention on renal biomarkers associated with diabetic nephropathy. | Dietary supplement | Placebo Cookie Group |
Primary outcome
Change in MMP-9 and NGAL Levels in Diabetic Patients with Early Renal Dysfunction
Time frame: Baseline and 12 weeks
This measure evaluates the change in serum levels of matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL) in diabetic patients with early renal dysfunction after 12 weeks of intervention. MMP-9 is associated with renal inflammation and extracellular matrix remodeling, while NGAL is a marker of tubular injury and oxidative stress. Blood samples will be collected at baseline and at the end of the 12-week period, and serum levels of MMP-9 and NGAL will be quantified using validated ELISA kits. This assessment aims to determine the potential effects of the Piper crocatum intervention on renal health by observing significant changes in these biomarkers
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2024.
- Background: PubMed 24612734Serra R, Grande R, Butrico L, Buffone G, Calio FG, Squillace A, Rizzo BA, Massara M, Spinelli F, Ferrarese AG, de Caridi G, Gallelli L, de Franciscis S. Effects of a new nutraceutical substance on clinical and molecular parameters in patients with chronic venous ulceration. Int Wound J. 2016 Feb;13(1):88-96. doi: 10.1111/iwj.12240. Epub 2014 Feb 25.
- Background: PubMed 30568032Rojas-Quintero J, Wang X, Tipper J, Burkett PR, Zuniga J, Ashtekar AR, Polverino F, Rout A, Yambayev I, Hernandez C, Jimenez L, Ramirez G, Harrod KS, Owen CA. Matrix metalloproteinase-9 deficiency protects mice from severe influenza A viral infection. JCI Insight. 2018 Dec 20;3(24):e99022. doi: 10.1172/jci.insight.99022.
- Background: PubMed 32225016Rodriguez-Sanchez E, Navarro-Garcia JA, Aceves-Ripoll J, Abarca-Zabalia J, Susmozas-Sanchez A, Bada-Bosch T, Hernandez E, Merida-Herrero E, Andres A, Praga M, Fernandez-Ruiz M, Aguado JM, Segura J, Ruilope LM, Ruiz-Hurtado G. Variations in Circulating Active MMP-9 Levels During Renal Replacement Therapy. Biomolecules. 2020 Mar 26;10(4):505. doi: 10.3390/biom10040505.
- Background: PubMed 38675538Latronico T, Petraglia T, Sileo C, Bilancia D, Rossano R, Liuzzi GM. Inhibition of MMP-2 and MMP-9 by Dietary Antioxidants in THP-1 Macrophages and Sera from Patients with Breast Cancer. Molecules. 2024 Apr 10;29(8):1718. doi: 10.3390/molecules29081718.
- Background: PubMed 37868469Kumar M, Dev S, Khalid MU, Siddenthi SM, Noman M, John C, Akubuiro C, Haider A, Rani R, Kashif M, Varrassi G, Khatri M, Kumar S, Mohamad T. The Bidirectional Link Between Diabetes and Kidney Disease: Mechanisms and Management. Cureus. 2023 Sep 20;15(9):e45615. doi: 10.7759/cureus.45615. eCollection 2023 Sep.
- Background: PubMed 31121851Jones JI, Nguyen TT, Peng Z, Chang M. Targeting MMP-9 in Diabetic Foot Ulcers. Pharmaceuticals (Basel). 2019 May 22;12(2):79. doi: 10.3390/ph12020079.
- Results publication: PubMed 34867030Setyawati 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.
- Results publication: PubMed 38422498Setyawati 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.
- Results publication: PubMed 33775157Papadopoulou-Marketou N, Whiss PA, Eriksson AC, Hyllienmark L, Papassotiriou I, Wahlberg J. Plasma levels of tissue inhibitor of metalloproteinase-1 in patients with type 1 diabetes mellitus associate with early diabetic neuropathy and nephropathy. Diab Vasc Dis Res. 2021 Mar-Apr;18(2):14791641211002470. doi: 10.1177/14791641211002470.
- Results publication: PubMed 29615682Pan SC, Li CY, Kuo CY, Kuo YZ, Fang WY, Huang YH, Hsieh TC, Kao HY, Kuo Y, Kang YR, Tsai WC, Tsai ST, Wu LW. The p53-S100A2 Positive Feedback Loop Negatively Regulates Epithelialization in Cutaneous Wound Healing. Sci Rep. 2018 Apr 3;8(1):5458. doi: 10.1038/s41598-018-23697-5.
- Results publication: PubMed 29707087Nevo A, Armaly Z, Abd El Kadir A, Douvdevani A, Tovbin D. Elevated Neutrophil Gelatinase Lipocalin Levels Are Associated With Increased Oxidative Stress in Hemodialysis Patients. J Clin Med Res. 2018 Jun;10(6):461-465. doi: 10.14740/jocmr3360w. Epub 2018 Apr 13.
- Results publication: PubMed 37101162Danquah M, Owiredu WKBA, Jnr BAE, Serwaa D, Odame Anto E, Peprah MO, Obirikorang C, Fondjo LA. Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for detection of renal failure in hypertensives: a case-control study in a regional hospital in Ghana. BMC Nephrol. 2023 Apr 26;24(1):114. doi: 10.1186/s12882-023-03120-6.
- This study examines the effect of Piper crocatum-enriched Golden Rice cookies on diabetic foot ulcer prevention by modulating MMP-9 levels. The cookies are designed to reduce inflammation and support diabetic foot health through dietary interventionLink provided by the sponsor.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be routinely shared to protect participant privacy and confidentiality. However, data may be made available to qualified researchers upon request, subject to approval by the study's principal investigator and in compliance with relevant privacy regulations and institutional policies.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Piper crocatum Extract Cookie in people with Early Renal Dysfunction in Diabetes and Diabetic Nephropathy, run by Hasanuddin University at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in MMP-9 and NGAL Levels in Diabetic Patients with Early Renal Dysfunction (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06676124, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2024.