Radiofrequency Ablation for ADPKD Blood Pressure and Disease Progression Control

NCT01932450 | Unknown Phase 2 DMC

• 1 other identifier: CZKIPLA-ADPKD-001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, open-label single-center study investigates the efficacy and safety of bilateral renal artery sympathetic denervation by catheter-based radiofrequency ablation on blood pressure and disease progression control in autosomal dominant polycystic kidney disease(ADPKD). The total number of study subjects will be 100. All of them have diagnosed with ADPKD and hypertension. Patients will be randomized 1:1 (50 with radiofrequency ablation(RFA), 50 only with drugs). Change in average office-based measurements of systolic blood pressure(SBP), average 24-hour systolic blood pressure by ambulatory blood pressure monitoring (ABPM) , incidence of office systolic blood pressure reductions of ≥10, ≥15 and ≥20 mm Hg , office diastolic blood pressure (DBP), number and dosage of blood pressure tablets, total kidney volume (TKV), total cyst volume (TCV), pain related to cystic kidneys and renal function, will be assessed at 12 months of follow-up. The safety variables will be assessed at every visit of follow-up.

Conditions

Autosomal Dominant Polycystic Kidney Disease; Hypertension

Keywords

hypertension; radiofrequency ablation; autosomal dominant polycystic kidney disease

Outcome Measures

Primary Outcomes (1)

• office-based measurements of systolic blood pressure

  Between-group change in average office-based measurements of systolic blood pressure from baseline to 12 months after randomization and One-time standard bilateral renal sympathetic denervation by catheter-based radiofrequency ablation.

  baseline and 12 months (day 360±14)

Secondary Outcomes (16)

• 24-hour systolic blood pressure by ambulatory blood pressure monitoring (ABPM)

  baseline and 12 months (day 360±14)

• Incidence of office systolic blood pressure reduction

  baseline and 12 months (day 360±14)

• office diastolic blood pressure

  baseline and 12 months (day 360±14)

• number and dosage of blood pressure tablets

  baseline and 12 months (day 360±14)

• estimated Glomerular Filtration Rate(eGFR)

  baseline and 12 months (day 360±14)

Study Arms (2)

renal sympathetic denervation

EXPERIMENTAL

One-time standard bilateral renal sympathetic denervation by catheter-based radiofrequency ablation and using antihypertensive drugs which at least include an angiotensin converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB).

Procedure: renal sympathetic denervation; Drug: antihypertensive drugs

antihypertensive drugs

ACTIVE COMPARATOR

Blood pressure control in ADPKD patients with hypertension only using antihypertensive drugs which at least include an angiotensin converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB)

Drug: antihypertensive drugs

Interventions

renal sympathetic denervation PROCEDURE

One-time standard Catheter-based renal sympathetic denervation will be performed in both renal arteries by radiofrequency ablation.

Also known as: Percutaneous radiofrequency ablation of renal nerves, Transcatheter renal denervation, renal denervation, renal ablation

renal sympathetic denervation

antihypertensive drugs DRUG

antihypertensive drugs have been used from baseline in patients, and will be modified by patient's blood pressure.

antihypertensive drugs; renal sympathetic denervation

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with ADPKD.
• Having hypertension, defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg, and currently using 2 antihypertensive drugs and receiving a stable antihypertensive treatment regimen without change in dose or medication in the previous 30 days.
• Male and female patients 20 years to 60 years of age.
• Glomerular Filtration Rate (GFR) ≥30 ml/min/1.73 m2, estimated from serum creatinine using the Chronic Kidney Disease Epidemiology collaboration(CKD-EPI) equation.
• Have followed-up kidney and cyst volume at least 6 months in Shanghai Changzheng Hospital.
• Signed Informed Consent after being informed.

You may not qualify if:

• Documented renal vascular disease.
• Congenital absence of a kidney.
• Systemic illness with renal involvement.
• Spot urine albumin-to-creatinine ratio of \>0.5 g/g and/or findings suggestive of kidney disease other than ADPKD.
• Contraindications to the catheter-based renal denervation procedure by RFA, including allergy to radioiodinated contrast agents. Anatomical abnormalities of the renal arteries which preclude RFA: presence in either kidneys of multiple main renal arteries, main renal artery stenosis \>50%, or main renal arteries of \<4 mm in diameter or \<20 mm in length.
• Contraindications on ethical grounds.
• Women who are pregnant or breast feeding.
• Intention to become pregnant during the course of the study.
• Lack of safe contraception: Female subjects of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases (Female subjects who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential).
• Other clinically significant concomitant disease states (hepatic dysfunction, cardiovascular disease, metastatic cancer).
• Known or suspected non-compliance, drug or alcohol abuse.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia or confusional state of the subject.
• Participation in another study with investigational drug within the 30 days preceding and during the present study.
• Previous enrolment into the current study.
• Enrolment of the investigator, his/her family members, employees and other dependent persons.

Sponsors & Collaborators

• Mei changlin: lead

Study Sites (1)

Department of Nephrology, Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, 200003, China

RECRUITING

Related Publications (39)

• 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.

  PMID: 17434405 BACKGROUND

• Harris PC, Torres VE. Polycystic kidney disease. Annu Rev Med. 2009;60:321-37. doi: 10.1146/annurev.med.60.101707.125712.

  PMID: 18947299 BACKGROUND

• Grantham JJ. Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med. 2008 Oct 2;359(14):1477-85. doi: 10.1056/NEJMcp0804458. No abstract available.

  PMID: 18832246 BACKGROUND

• Chang MY, Ong AC. Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and treatment. Nephron Physiol. 2008;108(1):p1-7. doi: 10.1159/000112495. Epub 2007 Dec 13.

  PMID: 18075279 BACKGROUND

• Neumann J, Ligtenberg G, Klein IH, Blankestijn PJ. Pathogenesis and treatment of hypertension in polycystic kidney disease. Curr Opin Nephrol Hypertens. 2002 Sep;11(5):517-21. doi: 10.1097/00041552-200209000-00007.

  PMID: 12187316 BACKGROUND

• Chapman AB, Johnson AM, Rainguet S, Hossack K, Gabow P, Schrier RW. Left ventricular hypertrophy in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1997 Aug;8(8):1292-7. doi: 10.1681/ASN.V881292.

  PMID: 9259356 BACKGROUND

• Ecder T, Schrier RW. Hypertension in autosomal-dominant polycystic kidney disease: early occurrence and unique aspects. J Am Soc Nephrol. 2001 Jan;12(1):194-200. doi: 10.1681/ASN.V121194. No abstract available.

  PMID: 11134267 BACKGROUND

• Chapman AB, Stepniakowski K, Rahbari-Oskoui F. Hypertension in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010 Mar;17(2):153-63. doi: 10.1053/j.ackd.2010.01.001.

  PMID: 20219618 BACKGROUND

• Cerasola G, Vecchi M, Mule G, Cottone S, Mangano MT, Andronico G, Contorno A, Parrino I, Renda F, Pavone G. Sympathetic activity and blood pressure pattern in autosomal dominant polycystic kidney disease hypertensives. Am J Nephrol. 1998;18(5):391-8. doi: 10.1159/000013382.

  PMID: 9730562 BACKGROUND

• Klein IHHT, Ligtenberg G, Oey PL, Koomans HA, Blankestijn PJ. Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension. J Am Soc Nephrol. 2001 Nov;12(11):2427-2433. doi: 10.1681/ASN.V12112427.

  PMID: 11675419 BACKGROUND

• Schrier RW. Hypertension and autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2011 Jun;57(6):811-3. doi: 10.1053/j.ajkd.2011.02.379. No abstract available.

  PMID: 21601126 BACKGROUND

• Chapman AB, Torres VE, Perrone RD, Steinman TI, Bae KT, Miller JP, Miskulin DC, Rahbari Oskoui F, Masoumi A, Hogan MC, Winklhofer FT, Braun W, Thompson PA, Meyers CM, Kelleher C, Schrier RW. The HALT polycystic kidney disease trials: design and implementation. Clin J Am Soc Nephrol. 2010 Jan;5(1):102-9. doi: 10.2215/CJN.04310709.

  PMID: 20089507 BACKGROUND

• Torres VE, Chapman AB, Perrone RD, Bae KT, Abebe KZ, Bost JE, Miskulin DC, Steinman TI, Braun WE, Winklhofer FT, Hogan MC, Oskoui FR, Kelleher C, Masoumi A, Glockner J, Halin NJ, Martin DR, Remer E, Patel N, Pedrosa I, Wetzel LH, Thompson PA, Miller JP, Meyers CM, Schrier RW; HALT PKD Study Group. Analysis of baseline parameters in the HALT polycystic kidney disease trials. Kidney Int. 2012 Mar;81(6):577-85. doi: 10.1038/ki.2011.411. Epub 2011 Dec 28.

  PMID: 22205355 BACKGROUND

• Gattone VH 2nd, Siqueira TM Jr, Powell CR, Trambaugh CM, Lingeman JE, Shalhav AL. Contribution of renal innervation to hypertension in rat autosomal dominant polycystic kidney disease. Exp Biol Med (Maywood). 2008 Aug;233(8):952-7. doi: 10.3181/0802-RM-54. Epub 2008 May 14.

  PMID: 18480417 BACKGROUND

• Chapuis O, Sockeel P, Pallas G, Pons F, Jancovici R. Thoracoscopic renal denervation for intractable autosomal dominant polycystic kidney disease-related pain. Am J Kidney Dis. 2004 Jan;43(1):161-3. doi: 10.1053/j.ajkd.2003.07.026.

  PMID: 14712440 BACKGROUND

• Valente JF, Dreyer DR, Breda MA, Bennett WM. Laparoscopic renal denervation for intractable ADPKD-related pain. Nephrol Dial Transplant. 2001 Jan;16(1):160. doi: 10.1093/ndt/16.1.160. No abstract available.

  PMID: 11209012 BACKGROUND

• Hogan MC, Norby SM. Evaluation and management of pain in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010 May;17(3):e1-e16. doi: 10.1053/j.ackd.2010.01.005.

  PMID: 20439087 BACKGROUND

• MORRISSEY DM, BROOKES VS, COOKE WT. Sympathectomy in the treatment of hypertension; review of 122 cases. Lancet. 1953 Feb 28;1(6757):403-8. doi: 10.1016/s0140-6736(53)91589-x. No abstract available.

  PMID: 13024041 BACKGROUND

• SMITHWICK RH, THOMPSON JE. Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc. 1953 Aug 15;152(16):1501-4. doi: 10.1001/jama.1953.03690160001001. No abstract available.

  PMID: 13061307 BACKGROUND

• EVELYN KA, SINGH MM, CHAPMAN WP, PERERA GA, THALER H. Effect of thoracolumbar sympathectomy on the clinical course of primary (essential) hypertension. A ten-year study of 100 sympathectomized patients compared with individually matched, symptomatically treated control subjects. Am J Med. 1960 Feb;28:188-221. doi: 10.1016/0002-9343(60)90184-4. No abstract available.

  PMID: 13821037 BACKGROUND

• Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med. 2009 Aug 27;361(9):932-4. doi: 10.1056/NEJMc0904179. No abstract available.

  PMID: 19710497 BACKGROUND

• Schlaich MP, Hering D, Sobotka P, Krum H, Lambert GW, Lambert E, Esler MD. Effects of renal denervation on sympathetic activation, blood pressure, and glucose metabolism in patients with resistant hypertension. Front Physiol. 2012 Feb 2;3:10. doi: 10.3389/fphys.2012.00010. eCollection 2012.

  PMID: 22347190 BACKGROUND

• Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009 Apr 11;373(9671):1275-81. doi: 10.1016/S0140-6736(09)60566-3. Epub 2009 Mar 28.

  PMID: 19332353 BACKGROUND

• Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011 May;57(5):911-7. doi: 10.1161/HYPERTENSIONAHA.110.163014. Epub 2011 Mar 14.

  PMID: 21403086 BACKGROUND

• Symplicity HTN-2 Investigators; Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010 Dec 4;376(9756):1903-9. doi: 10.1016/S0140-6736(10)62039-9. Epub 2010 Nov 17.

  PMID: 21093036 BACKGROUND

• Kandzari DE, Bhatt DL, Sobotka PA, O'Neill WW, Esler M, Flack JM, Katzen BT, Leon MB, Massaro JM, Negoita M, Oparil S, Rocha-Singh K, Straley C, Townsend RR, Bakris G. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 Trial. Clin Cardiol. 2012 Sep;35(9):528-35. doi: 10.1002/clc.22008. Epub 2012 May 9.

  PMID: 22573363 BACKGROUND

• Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA, Sobotka PA, Bohm M, Cremers B, Esler MD, Schlaich MP. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012 Jul;23(7):1250-7. doi: 10.1681/ASN.2011111062. Epub 2012 May 17.

  PMID: 22595301 BACKGROUND

• Casale P, Meyers K, Kaplan B. Follow-up for laparoscopic renal denervation and nephropexy for autosomal dominant polycystic kidney disease-related pain in pediatrics. J Endourol. 2008 May;22(5):991-3. doi: 10.1089/end.2007.0359.

  PMID: 18370613 BACKGROUND

• Schlaich MP, Krum H, Esler MD. New therapeutic approaches to resistant hypertension. Curr Hypertens Rep. 2010 Aug;12(4):296-302. doi: 10.1007/s11906-010-0119-1.

  PMID: 20509010 BACKGROUND

• Serra AL, Poster D, Kistler AD, Krauer F, Raina S, Young J, Rentsch KM, Spanaus KS, Senn O, Kristanto P, Scheffel H, Weishaupt D, Wuthrich RP. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010 Aug 26;363(9):820-9. doi: 10.1056/NEJMoa0907419. Epub 2010 Jun 26.

  PMID: 20581391 BACKGROUND

• Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.

  PMID: 8598068 BACKGROUND

• Celermajer DS. Testing endothelial function using ultrasound. J Cardiovasc Pharmacol. 1998;32 Suppl 3:S29-32.

  PMID: 9883744 BACKGROUND

• Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ; Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005 Jan;23(1):7-17. doi: 10.1097/00004872-200501000-00004.

  PMID: 15643116 BACKGROUND

• Gemignani V, Bianchini E, Faita F, Giannarelli C, Plantinga Y, Ghiadoni L, Demi M. Ultrasound measurement of the brachial artery flow-mediated dilation without ECG gating. Ultrasound Med Biol. 2008 Mar;34(3):385-91. doi: 10.1016/j.ultrasmedbio.2007.08.006. Epub 2007 Oct 26.

  PMID: 17964069 BACKGROUND

• Sudano I, Flammer AJ, Periat D, Enseleit F, Hermann M, Wolfrum M, Hirt A, Kaiser P, Hurlimann D, Neidhart M, Gay S, Holzmeister J, Nussberger J, Mocharla P, Landmesser U, Haile SR, Corti R, Vanhoutte PM, Luscher TF, Noll G, Ruschitzka F. Acetaminophen increases blood pressure in patients with coronary artery disease. Circulation. 2010 Nov 2;122(18):1789-96. doi: 10.1161/CIRCULATIONAHA.110.956490. Epub 2010 Oct 18.

  PMID: 20956208 BACKGROUND

• Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O'Rourke M; CAFE Investigators; Anglo-Scandinavian Cardiac Outcomes Trial Investigators; CAFE Steering Committee and Writing Committee. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006 Mar 7;113(9):1213-25. doi: 10.1161/CIRCULATIONAHA.105.595496. Epub 2006 Feb 13.

  PMID: 16476843 BACKGROUND

• Pannier B, Guerin A, London G, Asmar R, Safar M; REASON Study. [Combination of low-dose perindopril/indapamide versus atenolol in the hypertensive patient. Effects on systolic pressure and arterial hemodynamics. REASON Study]. Arch Mal Coeur Vaiss. 2002 Sep;95 Spec No 6:11-6. French.

  PMID: 12407781 BACKGROUND

• Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H; European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006 Nov;27(21):2588-605. doi: 10.1093/eurheartj/ehl254. Epub 2006 Sep 25.

  PMID: 17000623 BACKGROUND

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

  PMID: 39356039 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Hypertension

Interventions

Antihypertensive Agents

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Changlin Mei, MD

  Nephrology Department of Shanghai Changzheng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Changlin Mei, MD

CONTACT

+86 21 81885391; chlmei1954@126.com

Yiyi Ma, Master

CONTACT

+8613661679863; dukemm@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, Professor, The director of Nephrology department and Internal Medicine department

Study Record Dates

• First Submitted: August 18, 2013
• First Posted: August 30, 2013
• Study Start: August 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: July 1, 2015
• Last Updated: September 25, 2014

Record last verified: 2014-09

Locations

CN (1)