Dietary Modulation of Urinary MCP-1 in ADPKD
lauantai 13. kesäkuuta 2026 päivittänyt: Elad Nizri, Assaf-Harofeh Medical Center
Open Labeled , Randomized, Controlled, Crossover Trial on the Effect of a Carbohydrate Restricted Plant Dominant Diet on MCP-1 Mediated Inflammatory Signaling in Autosomal Dominant Polycystic Kidney Disease
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst growth and declining kidney function. Inflammatory pathways, including those mediated by monocyte chemoattractant protein-1 (MCP-1), are increasingly recognized as contributors to disease progression. Metabolic alterations in cystic epithelial cells may influence inflammatory signaling, suggesting a potential role for dietary interventions targeting metabolic pathways.
This study is a prospective, randomized, open-label crossover trial designed to evaluate the effect of a carbohydrate restricted, plant dominant dietary intervention on urinary MCP-1 levels in adults with ADPKD. Participants will be randomized to one of two sequences: dietary intervention followed by usual diet, or usual diet followed by dietary intervention, with a washout period between study phases. Each study period will last 12 weeks.
The primary objective is to assess within subject differences in urinary MCP-1/creatinine ratio between the dietary intervention and usual diet conditions. Secondary outcomes include measures of metabolic parameters, insulin resistance, dietary adherence, and safety.
This study aims to explore whether a structured dietary approach may influence intrarenal inflammatory activity in ADPKD and provide preliminary data to inform future interventional studies.
Tutkimuksen yleiskatsaus
Tila
Ei vielä rekrytointia
Opintotyyppi
Interventio
Ilmoittautuminen (Arvioitu)
36
Vaihe
- Ei sovellettavissa
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskeluyhteys
- Nimi: ELAD NIZRI, MD
- Puhelinnumero: 972-502932222
- Sähköposti: nizrielad@gmail.com
Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Ei
Kuvaus
Inclusion Criteria:
- Age ≥18
- Diagnosis of ADPKD based on established clinical or genetic criteria (PKD 1/PKD2)
- Estimated glomerular filtration rate (eGFR) between 45 and 90 mL/min/1.73 m²
- Mayo Imaging Classification class 1C-1E based on MRI-derived height-adjusted total kidney volume.
- Stable kidney function, defined as no acute kidney injury and no decline in eGFR >20% within the preceding 3 months
- Stable antihypertensive and chronic medications for at least 4 weeks prior to enrollment
- Ability and willingness to adhere to the prescribed dietary intervention
- Ability to provide written informed consent
Exclusion Criteria:
- eGFR <45 mL/min/1.73 m² or requirement for dialysis
- History of kidney transplantation
- Significant albuminuria, defined as urine albumin to creatinine ratio (UACR) >300 mg/g
- Poorly controlled or unstable diabetes mellitus (e.g., HbA1c >8% or clinically significant glycemic variability or frequent hypoglycemia)
- Use of Tolvaptan at the time of screening or within the study period
- Current adherence to a ketogenic or carbohydrate restricted diet
- Unintentional weight loss >5% within the preceding 3 months
- Active infection, inflammatory disease, or malignancy that may influence inflammatory markers
- Current use of systemic corticosteroids or immunosuppressive therapy
- Active or symptomatic nephrolithiasis
- Serum bicarbonate <20 mmol/L
- Pregnancy or breastfeeding
- Known eating disorder or condition limiting adherence to dietary interventions
- Participation in another interventional study within the previous 3 months
- Any condition that, in the opinion of the investigators, would interfere with study participation or interpretation of results
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Perustiede
- Jako: Satunnaistettu
- Inventiomalli: Crossover-tehtävä
- Naamiointi: Yksittäinen
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
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Kokeellinen: Sequence A: Dietary Intervention → Usual Diet
Participants receive a carbohydrate restricted, plant dominant diet for 12 weeks, followed by a washout period and then usual diet for 12 weeks.
|
A structured dietary intervention targeting approximately 20% of total daily energy intake from carbohydrates (range 15-25%), with a plant dominant composition.
Energy and protein intake are prescribed based on adjusted body weight.
The intervention is not ketogenic and is not intended to induce nutritional ketosis.
Participants receive individualized dietary counseling and ongoing support from a registered dietitian.
Participants continue their habitual diet without specific dietary intervention or structured nutritional guidance.
|
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Kokeellinen: Sequence B: Usual Diet → Dietary Intervention
Participants follow their usual diet for 12 weeks, followed by a washout period and then the dietary intervention for 12 weeks.
|
A structured dietary intervention targeting approximately 20% of total daily energy intake from carbohydrates (range 15-25%), with a plant dominant composition.
Energy and protein intake are prescribed based on adjusted body weight.
The intervention is not ketogenic and is not intended to induce nutritional ketosis.
Participants receive individualized dietary counseling and ongoing support from a registered dietitian.
Participants continue their habitual diet without specific dietary intervention or structured nutritional guidance.
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Change in Urinary MCP-1/Creatinine Ratio
Aikaikkuna: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Urinary MCP-1 levels will be measured in first morning urine samples and normalized to urine creatinine (MCP-1/creatinine ratio).
For each study period, two samples will be collected within the final week (2-5 days apart), and the mean value will be used.
The primary outcome is the within subject difference in MCP-1/creatinine ratio between the dietary intervention and usual diet conditions.
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Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Association Between Carbohydrate Intake and MCP-1
Aikaikkuna: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
Mean carbohydrate intake during each study period will be calculated from repeated dietary assessments.
The association between carbohydrate intake and urinary MCP-1/creatinine ratio will be evaluated to explore a potential dose response relationship.
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Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Association Between Change in HOMA-IR and MCP-1
Aikaikkuna: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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The association between changes in insulin resistance (HOMA-IR) and changes in urinary MCP-1/creatinine ratio will be evaluated within individuals across study conditions.
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Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Dietary Adherence and MCP-1 Response
Aikaikkuna: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
Dietary adherence will be defined as the proportion of dietary assessments in which carbohydrate intake falls within the target range (15-25% of total energy intake).
The association between adherence and urinary MCP-1/creatinine ratio will be evaluated.
|
Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Change in Metabolic and Biochemical Parameters (Safety Outcomes)
Aikaikkuna: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Changes in selected metabolic and biochemical parameters, including serum bicarbonate, LDL cholesterol, and estimated glomerular filtration rate (eGFR), will be assessed between study conditions to evaluate the safety of the dietary intervention.
|
Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Mediation Analysis of Insulin Resistance and MCP-1
Aikaikkuna: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
Exploratory analysis to evaluate whether changes in insulin resistance (HOMA-IR) mediate the relationship between dietary intervention and urinary MCP-1/creatinine ratio using regression based mediation models.
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Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Gene Expression of CPT1A and ACOX1
Aikaikkuna: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Pre-specified exploratory analysis of gene expression of CPT1A and ACOX1, key regulators of fatty acid oxidation pathways, measured in peripheral blood samples.
Expression levels will be evaluated in relation to dietary intervention and changes in urinary MCP-1/creatinine ratio.
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Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Exploratory Analysis of the Gut Microbiome
Aikaikkuna: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
Exploratory analyses will evaluate changes in gut microbial composition associated with the dietary intervention.
Stool samples collected at baseline and at the end of each study period will undergo microbiome analysis.
Changes in microbial diversity and taxonomic composition will be explored and correlated with dietary adherence, urinary MCP-1 levels, and metabolic parameters.
Given the exploratory nature of these analyses and the limited sample size, findings will be considered hypothesis-generating.
|
Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
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Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Julkaisuja ja hyödyllisiä linkkejä
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Opi tärkeimmät päivämäärät
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Ensimmäinen lähetetty
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Ensimmäinen toimitettu, joka täytti QC-kriteerit
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Ensimmäinen Lähetetty (Todellinen)
Tiistai 16. kesäkuuta 2026
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Tiistai 16. kesäkuuta 2026
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
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Viimeksi vahvistettu
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Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Kiliopatiat
- Urogenitaaliset sairaudet
- Miesten urogenitaaliset sairaudet
- Munuaissairaudet
- Urologiset sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet
- Naisten virtsa- ja sukupuolielinten sairaudet ja raskauden komplikaatiot
- Geneettiset sairaudet, synnynnäiset
- Synnynnäiset poikkeavuudet
- Poikkeavuuksia, useita
- Munuaissairaudet, kystiset
- Munuaisten polykystiset sairaudet
- Synnynnäiset, perinnölliset ja vastasyntyneiden sairaudet ja poikkeavuudet
- Polysystinen munuainen, autosomaalinen dominantti
Muut tutkimustunnusnumerot
- 0090-26-ASF
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