Cholecalciferol (Vitamin D3) Therapy in Chronic Kidney Disease (CKD) Subjects

• ClinicalTrials.gov Identifier: NCT00427037
• Recruitment Status: Completed
• First Posted: January 26, 2007
• Results First Posted: March 12, 2009
• Last Update Posted: July 22, 2015
• Sponsor: Atlanta VA Medical Center
• Information provided by (Responsible Party): Vin Tangpricha, Atlanta VA Medical Center

Study Description

Brief Summary:

This is a 12 week pilot and feasibility study with an enrollment goal of 30 subjects. Half of the subjects will be randomized to vitamin D3 and the other half will receive a placebo. Subjects will be referred from the nutrition or renal clinic at Emory. CKD stage 3 and 4 patients will be eligible for participation if they have been determined to have vitamin D deficiency and are not on treatment with vitamin D or vitamin D analogues. Subjects will sign an informed consent form after reviewing the protocol in detail with the principal investigator. A questionnaire would collect information about dietary vitamin D intake, sunlight exposure, and any symptoms of vitamin D deficiency. The subject will have baseline levels of serum vitamin D (25-hydroxyvitamin D), parathyroid hormone (PTH), serum calcium and phosphate, creatinine and other markers of bone turnover. The questionnaires and the blood draws would be repeated on the 6th and 12th week of the study. Subjects will be given 12 pills of each containing either 50,000 IU vitamin D or placebo and asked to take one pill a week. They would be scheduled to return to the clinic after 6 weeks and blood measurements would be repeated. Subjects will be asked to revisit for their final visit at the 12th week when they would have their last blood draw and assessment.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease; Vitamin D Deficiency	Drug: Cholecalciferol; Drug: Placebo	Not Applicable

Detailed Description:

Vitamin D supplementation in reducing secondary hyperparathyroidism in chronic kidney disease patients, stage 3 and 4: A randomized, placebo controlled pilot study Problem of interest Chronic Kidney Disease (CKD) patients suffer from severe metabolic bone disease, which represents a formidable challenge to physicians. Defective vitamin D metabolism, and secondary parathyroid activation have been suggested as possible causes. Vitamin D is important for musculoskeletal health. Vitamin D can be obtained from the diet or made in the skin from exposure to sunlight, but it has to be converted by the kidneys into calcitriol, the active form in order to be effective. Decreased kidney mass in CKD patients causes reduced capability to convert vitamin D into calcitriol due to less 1-alpha hydroxylase enzyme levels. Current standard of care for patients with chronic renal disease is treatment with vitamin D analogues such as Rocaltrol or Hectoral. However, these medications have the potential to cause hypercalcemia. Studies have shown that calcitriol production becoming dependent on 25- hydroxyvitamin D availability in moderate CKD patients. There is speculation that there is still some "reserve" left for the generation of calcitriol from vitamin D in these patients.

The main question being posed in this study is:

Primary: Can a weekly high dose supplementation of cholecalciferol be effective in raising 25(OH)D levels in patients with CKD and can this reduce parathyroid hormone levels in pre-dialysis chronic kidney disease patients?

Study Design This is an 12 week pilot and feasibility study with an enrollment goal of 30 subjects. Half of the subjects will be randomized to vitamin D3 and the other half will receive a placebo. Subjects will be referred from the nutrition or renal clinic at Emory. CKD stage 3 and 4 patients will be eligible for participation if they have been determined to have vitamin D deficiency and are not on treatment with vitamin D or vitamin D analogues. Subjects will sign an informed consent form after reviewing the protocol in detail with the principal investigator. A questionnaire would collect information about dietary vitamin D intake, sunlight exposure, and any symptoms of vitamin D deficiency. The subject will have baseline levels of serum vitamin D (25-hydroxyvitamin D), parathyroid hormone (PTH), serum calcium and phosphate, creatinine and other markers of bone turnover. The questionnaires and the blood draws would be repeated on the 6th and 12th week of the study. Subjects will be given 12 pills of each containing either 50,000 IU vitamin D3 or placebo and asked to take one pill a week. They would be scheduled to return to the clinic after 6 weeks and blood measurements would be repeated. Subjects will be asked to revisit for their final visit at the 12th week when they would have their last blood draw and assessment.

Treatment This is a randomized control trial. Only half of the subjects will receive vitamin D treatment and the other half placebo. If at the end of the study, the subject is still vitamin D deficiency, they will be referred to an endocrinologist or to their primary doctor for treatment.

Scientific advancement If successful, this study would provide the necessary preliminary data in order to conduct a larger randomized controlled study supplementing vitamin D in chronic kidney disease patients. One potential area of study would be to see whether subjects supplemented with vitamin D were able to raise their active vitamin D levels using the "reserve" hydroxylase enzyme in the kidneys compared to those subjects who were just supplemented with a placebo. This study is necessary in order to determine whether weekly intake of a high dose vitamin D is sufficient to decrease the parathyroid hormone levels in the given time frame.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of Cholecalciferol (Vitamin D3) Therapy in Correcting Vitamin D Insufficiency and Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease: A Randomized, Placebo Controlled Pilot Study
• Study Start Date: December 2005
• Actual Primary Completion Date: July 2006
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo	Drug: Placebo; identical placebo pill orally by mouth; Other Name: D3
Active Comparator: Cholecalciferol; D3	Drug: Cholecalciferol; 50,000 IU weekly by mouth; Other Name: Vitamin D3 is cholecalciferol

Outcome Measures

Primary Outcome Measures :

1. 25-hydroxyvitamin D [ Time Frame: 3 months ]
   25-hydroxyvitamin D measured in serum by ELISA

Secondary Outcome Measures :

1. Bone Turnover Marker-CTX [ Time Frame: 12 weeks ]
   Blood levels of C-telopeptide

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 18-85
• CKD stage 3-4 (GFR 15-59 ml/min/1.73 m2 body surface area, calculated by using the MDRD Study equation GFR Calculator)
• serum 25(OH)D concentrations ≤ 30 ng/mL, and serum PTH levels >70 pg/mL documented within the last six months

Exclusion Criteria:

• History of liver failure (serum AST or ALT > 3-fold the upper limit of normal)
• requiring dialysis at any stage of the study
• history of intestinal malabsorption or chronic diarrhea
• serum calcium level (corrected for serum albumin) > 10.5 mg/dL
• calcium x phosphorus product >70
• treatment with more than 1000 IU of vitamin D per day, or current treatment with a vitamin D analogue or calcimimetic
• an anti-epileptic medication and other medications which can affect vitamin D metabolism (e.g., phenobarbital, phenytoin, rifampicin)

Contacts and Locations

Locations

United States, Georgia

Emory Clinic

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Atlanta VA Medical Center

Investigators

• Principal Investigator: Vin Tangpricha, M.D. Ph.D.; Emory University

More Information

Additional Information:

Medscape Link 

Publications of Results:

Chandra P, Binongo JN, Ziegler TR, Schlanger LE, Wang W, Someren JT, Tangpricha V. Cholecalciferol (vitamin D3) therapy and vitamin D insufficiency in patients with chronic kidney disease: a randomized controlled pilot study. Endocr Pract. 2008 Jan-Feb;14(1):10-7. doi: 10.4158/EP.14.1.10.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Alvarez JA, Law J, Coakley KE, Zughaier SM, Hao L, Shahid Salles K, Wasse H, Gutierrez OM, Ziegler TR, Tangpricha V. High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2012 Sep;96(3):672-9. doi: 10.3945/ajcn.112.040642. Epub 2012 Aug 1.

• Responsible Party: Vin Tangpricha, Principal Investigator, Atlanta VA Medical Center
• ClinicalTrials.gov Identifier: NCT00427037
• Other Study ID Numbers: Vitamin D-2006
• First Posted: January 26, 2007
• Results First Posted: March 12, 2009
• Last Update Posted: July 22, 2015
• Last Verified: July 2015

Keywords provided by Vin Tangpricha, Atlanta VA Medical Center:

Vitamin D deficiency; Chronic Kidney Disease

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Vitamin D Deficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Vitamin D; Cholecalciferol; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents