The Effect of Vitamin D Supplementation on Calcium Excretion in Thalassemia: a Dose Response Study

Thalassemia Major Clinical Trial

Official title:

The Effect of Vitamin D Supplementation on Calcium Excretion in Thalassemia: a Dose Response Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01323608
• Other study ID #: 1102011521
• Status: Not yet recruiting
• Phase: Phase 4
• First received: March 24, 2011
• Last updated: April 18, 2011
• Start date: June 2011
• Est. completion date: December 2014

Study information

• Verified date: April 2011
• Source: Weill Medical College of Cornell University
• Contact: Maria Vogiatzi, MD
• Phone: 212-746-3462
• Email: mvogiatz[@]med.cornell.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this pilot study is to determine the effect of various doses of vitamin D supplementation on vitamin D stores and calcium excretion in the urine in subjects with Thalassemia Major (TM). Subjects with TM are routinely placed on vitamin D supplements because they frequently have osteoporosis (a condition in which bone tissue thins and loses density and strength) and low vitamin D stores. The amount of vitamin D supplementation that is required to raise vitamin D stores in optimal levels is not known in TM, and will be determined in this study. Finally, a recent study in TM has linked blood vitamin D levels to urine calcium excretion, which is a risk factor for kidney stones. Therefore, we want to determine changes in calcium excretion with various vitamin D doses and with increasing vitamin D stores. We plan to test 3 doses of vitamin D for 3 months in children and adults with TM. Changes in vitamin D blood levels and urinary calcium will be determined. The results of this pilot study will be used in future studies that will examine the effect of various doses of vitamin D supplementation in the treatment of osteoporosis in TM.

Description:

Specific Aim: To determine the effect of various doses of vitamin D supplementation on serum concentration of 25 hydroxy vitamin D (25OHD) and urinary calcium excretion in adults and children with TM.

Hypothesis: Vitamin D supplementation at doses that result in serum 25OHD levels >30 ng/ml result in high rates of hypercalciuria (i.e. increased urinary calcium excretion) in children and adults with TM.

The pilot study will be performed at Weill Cornell Medical College, Payson 695.

• Children and adults with TM, will be divided into 4 groups: "standard" vitamin D dose (equivalent to 400 IU/day), "intermediate" vitamin D dose (equivalent to 1000 IU/day), "high" vitamin D dose (equivalent to 2,000 IU/day) and a "placebo" group that will receive an inactive ingredient. 10 subjects will be assigned to each group. The duration of the study will be 3 months.

• While some studies found no difference between vitamin D2 and D3, others suggest that vitamin D3 may be more advantageous in restoring 25 OHD concentrations. For these reasons, vitamin D3 will be used in this protocol.

• Study schedule with study interventions and frequencies is set out below (see table). All 4 groups will adhere to the same schedule. After obtaining consent, subjects will have a "Baseline Visit", which will include: 1) a complete physical examination; 2) laboratory evaluation that includes measurement of 25OHD, which is the major circulating form of vitamin D and reflects the body's vitamin D stores. Additional blood and urine samples will be obtained for measurement of urinary calcium excretion and serum Calcium and parathyroid hormone (PTH); and 3) Dietary calcium intake questionnaire. 4) Start of study medication.

• Subjects will then return every 2-4 weeks for routine blood transfusions and as required for the management of Thalassemia. To ensure compliance, study medications will be administered by study personnel during these routine visits. Vitamin D supplies will be packaged according to one week worth requirement, i.e. as 1,000 IU/day x 7days=7,000 IU for the "intermediate" vitamin D group. The dose that will be administered during these visits will depend on the interval between transfusions, i.e. 7,000 IU x 2weeks, for a subject of the "intermediate" dose who is transfused every two weeks.

• At the end of 3 month treatment, subjects will have a final visit, that is also scheduled to coincide with a routine transfusion visit. Subjects will have the same evaluation and procedures as in "Baseline Visit" : 1) a complete physical examination; 2) fasting laboratory evaluation that includes measurement of 25OHD, urinary calcium excretion and serum Calcium and PTH; and 3) Dietary calcium intake questionnaire.

• Subjects will be asked to take calcium supplementation at the dose of 500 mg daily for the 6-8 year old and 1,000 mg daily for the 9-18 year old subjects. This intervention will ensure adequate calcium intake in both groups.

All labs will be processed at the CTSC Core Lab. Study meds will be distributed by the central pharmacy. Investigational drug will be administered by study personnel during the transfusion visits to ensure compliance.

Eligible subjects will be assigned to a study group following a block type of enrollment. To ensure an equal, or near equal sex and age distribution, study groups will be matched according to sex and age. Half of the subjects in each group will be composed of pediatric subjects and the other half will be composed of adult subjects.

Study Schedule and Procedures:

• Baseline visit: Physical Exam, 25OHD, Intact PTH & Serum Calcium, 24 hr & spot urine collection for Ca/Crea, Calcium intake questionnaire, Vitamin D Supplementation/Placebo.

• Every 2-4 weeks: Administration of Vitamin D/Placebo

• 3 Month Visit: Physical Exam, 25OHD, Intact PTH & Serum Calcium, 24 hr & spot urine collection for Ca/Crea, Calcium intake questionnaire, and Vitamin D Supplementation/ Placebo.

Primary study endpoint:

Changes in 25OHD concentrations and calcium excretion with the various vitamin D3 doses will be determined at the end of the study and constitute the primary endpoints.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 60 Years

Eligibility

Inclusion Criteria:

• Thalassemia Major (TM)

• 25 OHD: 15-29 ng/ml

• Age 6 to 60 years

• Albumin corrected serum Calcium: Normal (8.5-10.5 mg/dl)

Exclusion Criteria:

• Other thalassemia syndromes

• 25 OHD concentrations < 15 ng/ml or =30 ng/ml

• Subjects younger than 6 years

• Hypoparathyroidism

• Abnormal albumin corrected serum Ca (i.e. total calcium <8.5 or > 10.5 mg/dl)

• Medications that may adversely affect vitamin D metabolism (anticonvulsants) or absorption

• End stage renal, heart, or liver disease

• History of Nephrolithiasis or Nephrocalcinosis

• Diseases associated with hypercalciuria (ie. Sarcoidosis, Cushing syndrome, and Wilson disease to name a few)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Beta-Thalassemia
• Thalassemia
• Thalassemia Major

Intervention

Drug:
• Vitamin D3
Vitamin D3 will be given at the equivalent of the following doses: 400, 1000, and 2000 IU/day.
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Weill Cornell Medical College	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vitamin D Dose Response Curve	To perform a dose response curve for vitamin D supplementation study and determine the relationship between vitamin D doses and serum 25OHD concentrations and urinary calcium excretion in children and adults with TM.	3 Months	Yes
Secondary	Vitamin D Dose Response Curve	To determine changes in serum calcium and PTH concentrations with various vitamin D doses	3 Months	Yes