ThinkZn: Zinc & Bone Health in Thalassemia: The Think Zinc Study

• Sponsor: UCSF Benioff Children's Hospital Oakland (Other)
• Overall Status: Completed
• CT.gov ID: NCT00459732
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Children's Hospital of Philadelphia (Other), University of California, San Francisco (Other)
• Enrollment: 45
• Locations: 3
• Arms: 2
• Duration (Months): 58.1
• Patients Per Site: 15
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to test whether zinc can improve bone health in young patients with thalassemia.

Condition or Disease	Intervention/Treatment	Phase
Thalassemia	Dietary Supplement: Zinc; Dietary Supplement: Placebo	N/A

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Zinc and Bone Metabolism in Thalassemia
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Capsule placebo capsule, similar in size, shape and color to zinc capsule, taken once daily for 18 months	Dietary Supplement: Placebo; Placebo capsule, identical to the zn capsule in size, shape and color, taken once daily for 18 months; Other Names: "sugar" pill
Active Comparator: Zinc (25 mg/d) 25 mg of elemental Zinc as zinc sulphate taken once daily for 18 months	Dietary Supplement: Zinc; 25 mg of elemental zinc as zinc sulphate take once daily for 18 months; Other Names: zinc sulphate elemental zinc

Outcome Measures

Primary Outcome Measures

1. 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

2. Change in Whole Body Bone Mineral Content (BMC) by DXA (Baseline to 18 Months) [Baseline to 18 months]

Secondary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital & Research Center, Oakland	Oakland	California	United States	94609
2	University of California, San Francisco	San Francisco	California	United States	94143
3	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• UCSF Benioff Children's Hospital Oakland
• National Heart, Lung, and Blood Institute (NHLBI)
• Children's Hospital of Philadelphia
• University of California, San Francisco

Investigators

• Principal Investigator: Ellen B. Fung, PhD, RD, UCSF Benioff Children's Hospital Oakland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UCSF Benioff Children's Hospital Oakland
• ClinicalTrials.gov Identifier: NCT00459732
• Other Study ID Numbers: 2004-106; K23HL076468; NCT00480415
• First Posted: Apr 12, 2007
• Last Update Posted: Dec 4, 2020
• Last Verified: Dec 1, 2020

• Keywords provided by UCSF Benioff Children's Hospital Oakland: zinc, thalassemia, bone mineral density
• Additional relevant MeSH terms: Thalassemia; Zinc; Zinc Sulfate

Study Results

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 Detail	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.

Arm/Group Title	Zinc	Placebo
Arm/Group Description	25 mg of zinc as zn sulfate taken daily	daily capsule similar in size/color to zn was taken daily by this group
Period Title: Overall Study
STARTED	23	17
COMPLETED	19	14
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Zinc	Placebo	Total
Arm/Group Description	25 mg of zinc as zn sulfate taken daily	daily capsule similar in size/color to zn was taken daily by this group	Total of all reporting groups
Overall Participants	23	17	40
Age (Count of Participants)
<=18 years	10 43.5%	9 52.9%	19 47.5%
Between 18 and 65 years	13 56.5%	8 47.1%	21 52.5%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	17.7 (5.6)	17.4 (4.9)	17.6 (5.3)
Sex: Female, Male (Count of Participants)
Female	12 52.2%	9 52.9%	21 52.5%
Male	11 47.8%	8 47.1%	19 47.5%
Region of Enrollment (participants) [Number]
United States	23 100%	17 100%	40 100%
Plasma Zinc (mcg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mcg/dL]	77 (11)	79 (14)	78 (12)
Spine Z-score (Z-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Z-score]	-1.9 (1.0)	-2.4 (1.1)	-2.1 (1.0)

Outcome Measures

1. Primary Outcome

Title	Change in Lumbar Spine Bone Mineral Density (BMD) by DXA (Baseline to 18 Months)
Description	Change in pa spine bone mineral density by DXA between baseline and 18 months
Time Frame	0 to 18 months

Outcome Measure Data

Analysis Population Description

Intention to treat analysis of all subjects who completed the protocol in each arm of the study (zinc vs. placebo).

Arm/Group Title	Zinc	Placebo
Arm/Group Description	25 mg of zinc as zn sulfate taken daily	daily capsule similar in size/color to zn was taken daily by this group
Measure Participants	18	14
Mean (Standard Deviation) [Percent Change]	5.9 (5.3)	1.5 (9.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zinc, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Change in Whole Body Bone Mineral Content (BMC) by DXA (Baseline to 18 Months)
Time Frame	Baseline to 18 months

Outcome Measure Data

Analysis Population Description

Intention to treat analysis in those who completed the 18 month timepoint (zinc vs. placebo)

Arm/Group Title	Zinc	Placebo
Arm/Group Description	25 mg of zinc as zn sulfate taken daily	daily capsule similar in size/color to zn was taken daily by this group
Measure Participants	17	14
Mean (Standard Deviation) [Percent change]	6.1 (6.1)	2.2 (9.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zinc, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	ANOVA
	Comments	Repeated measures

3. Secondary Outcome

Title	Osteocalcin, a Marker of Bone Formation
Description	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

Outcome Measure Data

Analysis Population Description

Intention to treat analysis

Arm/Group Title	Zinc	Placebo
Arm/Group Description	25 mg of zinc as zn sulfate taken daily	daily capsule similar in size/color to zn was taken daily by this group
Measure Participants	19	14
Mean (Standard Deviation) [ng/mL]	8.8 (17.1)	-4.3 (23.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zinc, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	ANCOVA
	Comments	Repeated measures analysis of variance adjusted for baseline osteocalcin level.

Adverse Events

Time Frame	Recorded between baseline and 18 month time point (end of study)
Adverse Event Reporting Description	Adverse events were collected at 5 timepoints, 3, 6, 12 and 18 months after start of supplementation.
Arm/Group Title	Zinc		Placebo
Arm/Group Description	25 mg of zinc as zn sulfate taken daily		daily capsule similar in size/color to zn was taken daily by this group
All Cause Mortality
	Zinc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Zinc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		1/17 (5.9%)
Cardiac disorders
Death	0/23 (0%)	0	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Zinc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/19 (89.5%)		8/14 (57.1%)
Blood and lymphatic system disorders
Fatigue	5/19 (26.3%)	6	5/14 (35.7%)	6
Gastrointestinal disorders
Nausea	10/19 (52.6%)	14	8/14 (57.1%)	10
Diarrhea	3/19 (15.8%)	7	5/14 (35.7%)	7
Stomach Upset	11/19 (57.9%)	13	8/14 (57.1%)	11
Nervous system disorders
Headache	8/19 (42.1%)	9	8/14 (57.1%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.