Dietary Modulation of Urinary MCP-1 in ADPKD
2026년 6월 13일 업데이트: 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.
연구 개요
상태
아직 모집하지 않음
연구 유형
중재적
등록 (추정된)
36
단계
- 해당 없음
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
- 이름: ELAD NIZRI, MD
- 전화번호: 972-502932222
- 이메일: nizrielad@gmail.com
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위
- 중재 모델: 크로스오버 할당
- 마스킹: 하나의
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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.
|
|
실험적: 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.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in Urinary MCP-1/Creatinine Ratio
기간: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
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.
|
Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Association Between Carbohydrate Intake and MCP-1
기간: 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.
|
Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
|
Association Between Change in HOMA-IR and MCP-1
기간: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
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.
|
Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
|
Dietary Adherence and MCP-1 Response
기간: 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)
|
|
Change in Metabolic and Biochemical Parameters (Safety Outcomes)
기간: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
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)
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Mediation Analysis of Insulin Resistance and MCP-1
기간: 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.
|
Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
|
Gene Expression of CPT1A and ACOX1
기간: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
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.
|
Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)
|
|
Exploratory Analysis of the Gut Microbiome
기간: 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)
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9. doi: 10.1007/BF00280883.
- Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T, Baptista G, Barazzoni R, Blaauw R, Coats A, Crivelli A, Evans DC, Gramlich L, Fuchs-Tarlovsky V, Keller H, Llido L, Malone A, Mogensen KM, Morley JE, Muscaritoli M, Nyulasi I, Pirlich M, Pisprasert V, de van der Schueren MAE, Siltharm S, Singer P, Tappenden K, Velasco N, Waitzberg D, Yamwong P, Yu J, Van Gossum A, Compher C; GLIM Core Leadership Committee; GLIM Working Group. GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community. Clin Nutr. 2019 Feb;38(1):1-9. doi: 10.1016/j.clnu.2018.08.002. Epub 2018 Sep 3.
- Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007 Apr 14;369(9569):1287-1301. doi: 10.1016/S0140-6736(07)60601-1.
- Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS; TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012 Dec 20;367(25):2407-18. doi: 10.1056/NEJMoa1205511. Epub 2012 Nov 3.
- Torres JA, Kruger SL, Broderick C, Amarlkhagva T, Agrawal S, Dodam JR, Mrug M, Lyons LA, Weimbs T. Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease. Cell Metab. 2019 Dec 3;30(6):1007-1023.e5. doi: 10.1016/j.cmet.2019.09.012. Epub 2019 Oct 17.
- Maroni BJ, Steinman TI, Mitch WE. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985 Jan;27(1):58-65. doi: 10.1038/ki.1985.10.
- Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL, Harmon AJ, Sundsbak JL, Bae KT, Chapman AB, Grantham JJ, Mrug M, Hogan MC, El-Zoghby ZM, Harris PC, Erickson BJ, King BF, Torres VE; CRISP Investigators. Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol. 2015 Jan;26(1):160-72. doi: 10.1681/ASN.2013101138. Epub 2014 Jun 5.
- Bouillanne O, Morineau G, Dupont C, Coulombel I, Vincent JP, Nicolis I, Benazeth S, Cynober L, Aussel C. Geriatric Nutritional Risk Index: a new index for evaluating at-risk elderly medical patients. Am J Clin Nutr. 2005 Oct;82(4):777-83. doi: 10.1093/ajcn/82.4.777.
- Kim H, Caulfield LE, Garcia-Larsen V, Steffen LM, Grams ME, Coresh J, Rebholz CM. Plant-Based Diets and Incident CKD and Kidney Function. Clin J Am Soc Nephrol. 2019 May 7;14(5):682-691. doi: 10.2215/CJN.12391018. Epub 2019 Apr 25.
- D'Alessandro C, Torreggiani M, Lippi F, Avesani C, Cupisti A, Piccoli GB. A Requiem for a Standardized Calculation of Ideal Body Weight in Chronic Kidney Disease? J Ren Nutr. 2026 Jan 15:S1051-2276(26)00006-3. doi: 10.1053/j.jrn.2025.12.007. Online ahead of print.
- Ryu H, Park HC, Kim H, Heo J, Kang E, Hwang YH, Cho JY, Lee KB, Oh YK, Oh KH, Ahn C. Bioelectrical impedance analysis as a nutritional assessment tool in Autosomal Dominant Polycystic Kidney Disease. PLoS One. 2019 Apr 4;14(4):e0214912. doi: 10.1371/journal.pone.0214912. eCollection 2019.
- Charles K, Lewis MJ, Montgomery E, Reid M. The 2021 Chronic Kidney Disease Epidemiology Collaboration Race-Free Estimated Glomerular Filtration Rate Equations in Kidney Disease: Leading the Way in Ending Disparities. Health Equity. 2024 Jan 12;8(1):39-45. doi: 10.1089/heq.2023.0038. eCollection 2024.
- Ludwig DS, Willett WC, Putt ME. Wash-in and washout effects: mitigating bias in short term dietary and other trials. BMJ. 2025 Apr 22;389:e082963. doi: 10.1136/bmj-2024-082963.
- Passey C. Reducing the Dietary Acid Load: How a More Alkaline Diet Benefits Patients With Chronic Kidney Disease. J Ren Nutr. 2017 May;27(3):151-160. doi: 10.1053/j.jrn.2016.11.006. Epub 2017 Jan 20.
- Karihaloo A, Koraishy F, Huen SC, Lee Y, Merrick D, Caplan MJ, Somlo S, Cantley LG. Macrophages promote cyst growth in polycystic kidney disease. J Am Soc Nephrol. 2011 Oct;22(10):1809-14. doi: 10.1681/ASN.2011010084. Epub 2011 Sep 15.
- Messchendorp AL, Meijer E, Boertien WE, Engels GE, Casteleijn NF, Spithoven EM, Losekoot M, Burgerhof JGM, Peters DJM, Gansevoort RT; DIPAK Consortium. Urinary Biomarkers to Identify Autosomal Dominant Polycystic Kidney Disease Patients With a High Likelihood of Disease Progression. Kidney Int Rep. 2017 Oct 14;3(2):291-301. doi: 10.1016/j.ekir.2017.10.004. eCollection 2018 Mar.
- Zheng D, Wolfe M, Cowley BD Jr, Wallace DP, Yamaguchi T, Grantham JJ. Urinary excretion of monocyte chemoattractant protein-1 in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2003 Oct;14(10):2588-95. doi: 10.1097/01.asn.0000088720.61783.19.
- Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res. 2009 Jun;29(6):313-26. doi: 10.1089/jir.2008.0027.
- Donadelli R, Abbate M, Zanchi C, Corna D, Tomasoni S, Benigni A, Remuzzi G, Zoja C. Protein traffic activates NF-kB gene signaling and promotes MCP-1-dependent interstitial inflammation. Am J Kidney Dis. 2000 Dec;36(6):1226-41. doi: 10.1053/ajkd.2000.19838.
- Burke SJ, Collier JJ. Transcriptional regulation of chemokine genes: a link to pancreatic islet inflammation? Biomolecules. 2015 May 26;5(2):1020-34. doi: 10.3390/biom5021020.
- Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell. 2017 Mar 9;168(6):960-976. doi: 10.1016/j.cell.2017.02.004.
- Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, Flask CA, Novick AC, Goldfarb DA, Kramer-Zucker A, Walz G, Piontek KB, Germino GG, Weimbs T. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5466-71. doi: 10.1073/pnas.0509694103. Epub 2006 Mar 27.
- Rowe I, Chiaravalli M, Mannella V, Ulisse V, Quilici G, Pema M, Song XW, Xu H, Mari S, Qian F, Pei Y, Musco G, Boletta A. Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy. Nat Med. 2013 Apr;19(4):488-93. doi: 10.1038/nm.3092. Epub 2013 Mar 24.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (추정된)
2026년 7월 10일
기본 완료 (추정된)
2029년 1월 1일
연구 완료 (추정된)
2029년 1월 1일
연구 등록 날짜
최초 제출
2026년 6월 9일
QC 기준을 충족하는 최초 제출
2026년 6월 13일
처음 게시됨 (실제)
2026년 6월 16일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2026년 6월 16일
QC 기준을 충족하는 마지막 업데이트 제출
2026년 6월 13일
마지막으로 확인됨
2026년 4월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 0090-26-ASF
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
미정
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .