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Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy

Information source: Massachusetts General Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Calciphylaxis; Calcific Uremic Arteriolopathy

Intervention: Vitamin K (Dietary Supplement); Placebo (Other)

Phase: N/A

Status: Recruiting

Sponsored by: Massachusetts General Hospital

Official(s) and/or principal investigator(s):
Sagar Nigwekar, MD, MMSc, Principal Investigator, Affiliation: Massachusetts General Hospital

Overall contact:
Sagar Nigwekar, MD, MMSc, Phone: 617 726 7872, Email: snigwekar@mgh.harvard.edu

Summary

Calcific uremic arteriolopathy a. k.a. calciphylaxis is a vascular calcification disorder seen in dialysis patients. Calcific uremic arteriolopathy has 60-80% one-year mortality and significant morbidity associated with non-healing and extremely painful skin lesions. At present, there is no effective treatment for calcific uremic arteriolopathy. Vitamin K is an important vitamin for inhibiting vascular calcification. It is known to increase the circulating levels of carboxylated Matrix Gla Protein, a potent inhibitor of vascular calcification. However, the effects of vitamin K supplementation in patients with calcific uremic arteriolopathy are unknown. The purpose of this study is to conduct a pilot randomized controlled trial to examine the effects of oral vitamin K supplementation on circulating levels of anti-calcification factor (carboxylated Matrix Gla Protein) and clinical outcomes in patients with calcific uremic arteriolopathy.

Clinical Details

Official title: Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Change from baseline in circulating MGP level at 12 weeks

Secondary outcome:

Change from baseline in pain at 12 weeks

Change from baseline in lesion size at 12 weeks

Detailed description: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a vascular calcification disorder associated with 60-80% one-year mortality and significant morbidity. CUA predominantly affects end-stage renal disease (ESRD) patients and presents with painful skin lesions. Although rare (prevalence: 4% in dialysis patients), the incidence of CUA is on the rise as shown by us and others. Mural calcification of dermal arterioles is the hallmark histological finding of CUA. However, there are significant gaps in the understanding of the pathophysiology and risk factors for CUA and there are no effective therapies. In animal models, vitamin K prevents vascular calcification by serving as a co-factor for Matrix Gla Protein (MGP) carboxylation, a process that converts decarboxylated-MGP (dc-MGP) to carboxylated-MGP (c-MGP). By inhibiting pro-calcification Bone Morphogenic Protein (BMP) ligands, c-MGP acts as a potent vascular calcification inhibitor. uc-MGP is inactive with no vascular calcification inhibitory properties. However, the effects of vitamin K administration on CUA remain unknown. Aim: To conduct a pilot randomized controlled trial (RCT) of oral vitamin K in CUA. The investigators will examine the following hypotheses: Hypothesis 1: Vitamin K therapy, when compared to placebo, increases carboxylated Matrix Gla Protein in chronic hemodialysis patients with CUA. Hypothesis 2: Vitamin K therapy can be safely administered in chronic hemodialysis patients with CUA. Hypothesis 3: Vitamin K therapy leads to improvement in CUA pain and average lesion size when compared to placebo in chronic hemodialysis patients. Study population and procedures: Twenty patients will be enrolled in this pilot RCT over the 2-year study period. Study Procedures: Patients meeting the eligibility criteria will be consented and randomized to receive either vitamin K (phylloquinone) 10 mg orally three times a week for a total of 12 weeks or identical appearing placebo. Follow-up will occur every 4 weeks during which information will be obtained regarding pain severity, number and size of CUA lesion (s), and adverse events. Blood samples will be taken at baseline and at 12-week follow-up. Sample processing and assays: Blood samples (plasma and serum, total 30 mL) will be taken at baseline and at 12-week follow-up.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Calcific uremic arteriolopathy (a. k.a. calciphylaxis)

Exclusion Criteria:

- Warfarin discontinuation contra-indicated (e. g. mechanical heart valve)

- Prior allergic reaction to vitamin K

- Prior history of venous thromboembolism

- Pregnancy and lactation

Locations and Contacts

Sagar Nigwekar, MD, MMSc, Phone: 617 726 7872, Email: snigwekar@mgh.harvard.edu

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
Sagar Nigwekar, MD, MMSc, Phone: 617-726-7872, Email: snigwekar@mgh.harvard.edu
Additional Information

Related publications:

Nigwekar SU, Brunelli SM, Meade D, Wang W, Hymes J, Lacson E Jr. Sodium thiosulfate therapy for calcific uremic arteriolopathy. Clin J Am Soc Nephrol. 2013 Jul;8(7):1162-70. doi: 10.2215/CJN.09880912. Epub 2013 Mar 21.

Nigwekar SU. An unusual case of nonhealing leg ulcer in a diabetic patient. South Med J. 2007 Aug;100(8):851-2.

Nigwekar SU, Wolf M, Sterns RH, Hix JK. Calciphylaxis from nonuremic causes: a systematic review. Clin J Am Soc Nephrol. 2008 Jul;3(4):1139-43. doi: 10.2215/CJN.00530108. Epub 2008 Apr 16. Review.

Nigwekar SU, Bhan I, Turchin A, Skentzos SC, Hajhosseiny R, Steele D, Nazarian RM, Wenger J, Parikh S, Karumanchi A, Thadhani R. Statin use and calcific uremic arteriolopathy: a matched case-control study. Am J Nephrol. 2013;37(4):325-32. doi: 10.1159/000348806. Epub 2013 Mar 21.

Strazzula L, Nigwekar SU, Steele D, Tsiaras W, Sise M, Bis S, Smith GP, Kroshinsky D. Intralesional sodium thiosulfate for the treatment of calciphylaxis. JAMA Dermatol. 2013 Aug;149(8):946-9. doi: 10.1001/jamadermatol.2013.4565.

Allegretti AS, Nazarian RM, Goverman J, Nigwekar SU. Calciphylaxis: a rare but fatal delayed complication of Roux-en-Y gastric bypass surgery. Am J Kidney Dis. 2014 Aug;64(2):274-7. doi: 10.1053/j.ajkd.2014.02.029. Epub 2014 Apr 29.

Nigwekar SU, Solid CA, Ankers E, Malhotra R, Eggert W, Turchin A, Thadhani RI, Herzog CA. Quantifying a rare disease in administrative data: the example of calciphylaxis. J Gen Intern Med. 2014 Aug;29 Suppl 3:S724-31. doi: 10.1007/s11606-014-2910-1.

Starting date: January 2015
Last updated: January 6, 2015

Page last updated: August 23, 2015

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