Thalassemia
Conditions
Keywords
zinc, thalassemia, bone mineral density
Brief summary
The purpose of this study is to test whether zinc can improve bone health in young patients with thalassemia.
Detailed description
The primary aim of this study is to determine if zinc supplementation improves bone health in young patients with thalassemia. Osteoporosis is a significant co-morbidity in patients with thalassemia which leads to decreased quality of life. The most effective way to prevent osteoporosis is to build strong, dense bones in the early years. A combination of disease, endocrine and nutritional factors likely contribute to the etiology of osteoporosis in this population. However, even well transfused patients with normal gonadal function who are supplemented with calcium have low bone mass. It is hypothesized that patients with thalassemia have low bone mass, in part, due to zinc deficiency. Sub-optimal zinc status has been identified in patients with thalassemia and zinc supplementation has been shown to improve linear growth. To test the primary hypothesis, an 18 month randomized placebo-controlled trial of zinc supplementation (25 mg Zn/day) vs. placebo will be conducted in 60 young patients (6-30 yrs) with thalassemia and low bone mass (spine BMD Z-score \<-1.0). Bone health, as estimated from measurements of bone mass (by DXA and pQCT) and markers of bone formation and resorption will be the primary outcome variables. This will be the first study to examine the effects of zinc. supplementation on bone health in patients with thalassemia. If zinc supplementation is found to have a clinically important effect, this simple, safe, non-invasive therapy could quickly become a part of the standard care of these young patients and improve overall health in children and adult patients with thalassemia
Interventions
DIETARY_SUPPLEMENTZinc
25 mg of elemental zinc as zinc sulphate take once daily for 18 months
DIETARY_SUPPLEMENTPlacebo
Placebo capsule, identical to the zn capsule in size, shape and color, taken once daily for 18 months
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Children's Hospital of Philadelphia
University of California, San Francisco
UCSF Benioff Children's Hospital Oakland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* 6 to 30 years of age * thalassemia * bone mineral density Z-score \< -1.0 (by DXA)
Exclusion criteria
* Bone marrow transplant recipient * Currently prescribed treatment for low bone mass other than calcium or vitamin D (e.g. calcitonin, bisphosphonates) * Currently prescribed zinc supplementation who are unable or unwilling to stop during this trial * Currently participating in another trial with a medication known to affect bone mineral density. * Chronic use of systemic corticosteroids * Untreated hypogonadism or growth hormone deficiency * Baseline serum copper \< 70 µg/dL * Baseline vitamin D-25OH \< 11 ng/mL * Pregnant or lactating at study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lumbar Spine Bone Mineral Density (BMD) by DXA (Baseline to 18 Months) | 0 to 18 months | Change in pa spine bone mineral density by DXA between baseline and 18 months |
| Change in Whole Body Bone Mineral Content (BMC) by DXA (Baseline to 18 Months) | Baseline to 18 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Osteocalcin, a Marker of Bone Formation | Baseline to 18 months | Absolute change in serum osteocalcin between 0 and 18 months, intention to treat analysis between the zinc and placebo groups |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 3 hematology clinics in the US between April, 2006 and May, 2008. 114 potentially eligible patients were screened, 43 were considered eligible and consented to participation.
Pre-assignment details
Following enrollment, prior to group assignment, subjects were screened for copper and vitamin D status. If serum copper was \<70ug/dL and/or 25OH vitamin D \<20ng/mL, they were placed on daily supplementation, 2 mg Cu/day and/or 1000 IU vitamin D/day.
Participants by arm
| Arm | Count |
|---|---|
| Zinc 25 mg of zinc as zn sulfate taken daily | 23 |
| Placebo daily capsule similar in size/color to zn was taken daily by this group | 17 |
| Total | 40 |
Baseline characteristics
| Characteristic | Placebo | Total | Zinc |
|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 19 Participants | 10 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 21 Participants | 13 Participants |
| Age, Continuous | 17.4 years STANDARD_DEVIATION 4.9 | 17.6 years STANDARD_DEVIATION 5.3 | 17.7 years STANDARD_DEVIATION 5.6 |
| Plasma Zinc | 79 mcg/dL STANDARD_DEVIATION 14 | 78 mcg/dL STANDARD_DEVIATION 12 | 77 mcg/dL STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 17 participants | 40 participants | 23 participants |
| Sex: Female, Male Female | 9 Participants | 21 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 19 Participants | 11 Participants |
| Spine Z-score | -2.4 Z-score STANDARD_DEVIATION 1.1 | -2.1 Z-score STANDARD_DEVIATION 1 | -1.9 Z-score STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 19 | 8 / 14 |
| serious Total, serious adverse events | 0 / 23 | 1 / 17 |
Outcome results
Primary
Change in Lumbar Spine Bone Mineral Density (BMD) by DXA (Baseline to 18 Months)
Change in pa spine bone mineral density by DXA between baseline and 18 months
Time frame: 0 to 18 months
Population: Intention to treat analysis of all subjects who completed the protocol in each arm of the study (zinc vs. placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zinc | Change in Lumbar Spine Bone Mineral Density (BMD) by DXA (Baseline to 18 Months) | 5.9 Percent Change | Standard Deviation 5.3 |
| Placebo | Change in Lumbar Spine Bone Mineral Density (BMD) by DXA (Baseline to 18 Months) | 1.5 Percent Change | Standard Deviation 9 |
p-value: 0.13ANOVA
Primary
Change in Whole Body Bone Mineral Content (BMC) by DXA (Baseline to 18 Months)
Time frame: Baseline to 18 months
Population: Intention to treat analysis in those who completed the 18 month timepoint (zinc vs. placebo)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zinc | Change in Whole Body Bone Mineral Content (BMC) by DXA (Baseline to 18 Months) | 6.1 Percent change | Standard Deviation 6.1 |
| Placebo | Change in Whole Body Bone Mineral Content (BMC) by DXA (Baseline to 18 Months) | 2.2 Percent change | Standard Deviation 9.2 |
p-value: 0.44ANOVA
Secondary
Osteocalcin, a Marker of Bone Formation
Absolute change in serum osteocalcin between 0 and 18 months, intention to treat analysis between the zinc and placebo groups
Time frame: Baseline to 18 months
Population: Intention to treat analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zinc | Osteocalcin, a Marker of Bone Formation | 8.8 ng/mL | Standard Deviation 17.1 |
| Placebo | Osteocalcin, a Marker of Bone Formation | -4.3 ng/mL | Standard Deviation 23.2 |
p-value: 0.16ANCOVA