The Effect of Vitamin D Supplementation on Calcium Excretion in Thalassemia: a Dose Response Study
| Status: | Completed |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 6 - 60 |
| Updated: | 4/2/2016 |
| Start Date: | June 2011 |
| End Date: | December 2014 |
| Contact: | Maria Vogiatzi, MD |
| Email: | mvogiatz@med.cornell.edu |
| Phone: | 212-746-3462 |
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.
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.
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.
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.
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)
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