Sickle Cell DiseasePhase 2ZnSCDNCT06260891
Zinc Supplementation in Sickle Cell Disease: A Precursor to the Think Zinc for Bones Trial
A Phase 2 study testing 25 mg/day zinc and 40 mg/day zinc in people with Sickle Cell Disease, run by University of California, San Francisco at 6 sites in United States.
Trial summary
The goal of this short term prospective Phase II study is to compare the effects of two alternate daily doses of zinc (25 and 40 mg/day) in 34 randomly assigned homozygous Sickle Cell Disease (SCD-SS) patients aged 15-40 years old. Read more about this study
- Who is it for?
- Ages 15 to 40 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- 25 mg/day zinc and 40 mg/day zinc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 6 sitesUnited States
- Study dates
- 14 Feb 2026to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: ≥ 15.0 to ≤ 40.0 years
- Diagnosis: SCD-SS or SCD-S Beta zero Thalassemia, in steady state (defined as a minimum of 2 weeks days following pain crisis)
- Male or Female
Who cannot join
- Taking any supplement containing zinc and unable/willing to stop for 3 months prior to study start
- 25-Hydroxy Vitamin D < 20 ng/mL
- On chronic transfusion therapy (defined as >8 Transfusions/year) and iron overloaded (defined as liver iron concentration > 7 mg/g OR average serum ferritin >4000 ug/L)
- Unable swallow pills or take daily supplement as instructed
- Currently participating in another investigational drug trial
- Prior diagnosis of chronic kidney disease (eGFR < 30 mL/min/1.73m2)
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Not yet recruiting
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Amy Shova, amy.shova@cchmc.org
Charles Quinn, MD
- Not yet recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Rania Mohamed, rania.mohamed@duke.edu
JJ Strouse, MD
- Not yet recruiting
Baylor College of Medicine
Houston, Texas, 77030
Batha Tariq, batha.tariq@bcm.edu
Venee Tubman, MD
- Recruiting
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Ellen Fung, PhD, 510-428-3885 ext. 4939, ellen.fung@ucsf.edu
Beth Anne Martin, beth.martin@ucsf.edu
- Not yet recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Jemimah Frempong, frempongj@chop.edu
Alexis Thompson, MD, PhD
- Not yet recruiting
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Prasanna Vardhan, pxv147@jefferson.edu
Sophie Lanzkron, MD
About this study
The goal of this short term prospective Phase II study is to compare the effects of two alternate daily doses of zinc (25 and 40 mg/day) in 34 randomly assigned homozygous Sickle Cell Disease (SCD-SS) patients aged 15-40 years old. The main question it aims to answer is: Which biomarkers are most responsive to zinc supplementation, and what is the maximum tolerated zinc dose that induces the desired changes in biomarkers of bone turnover? Participants will be recruited from 6 American Society Hematology Research Collaborative SCD Centers. Eligible SCD subjects will be invited to participate in the 16-week study, involving 2 baseline blood draws 4 weeks apart, followed by a 12-week zinc intervention. The findings from this study will be used to determine the dosage of zinc to be used in a larger, future study on the long term impact of zinc supplementation on bone health in SCD-SS.
Read the detailed description
The investigators propose a two-arm, double-blinded, Phase II study comparing the effects of two different daily doses of zinc (25 and 40 mg/day) in 34 patients with SCD-SS aged 15-40 years old, randomly assigned to either group. The aim of the study is to determine the maximum tolerated zinc dose that induces desired changes in rates of bone formation and resorption. The findings from this study will function as preliminary data for a future randomized clinical trial and provide a novel characterization of bone marker response to short term zinc supplementation in SCD that has not previously been described in the literature.
SCD is the most prevalent heritable disorder affecting red blood cells worldwide. It is an autosomal recessive genetic condition inherited at birth when a child receives two genes, one from each parent, coding for abnormal hemoglobin. The defective hemoglobin proteins characteristic of SCD give rise to sickle-shaped red blood cells causing serious health complications, including early onset bone morbidity. Over half of young adults with SCD have osteoporosis and are at increased risk for fracture.
Zinc, an essential trace mineral, is crucial for red cell stability, growth and bone metabolism. Zinc deficiency is reported frequently in patients with SCD and has been related to poor growth, increased vaso-occlusive crises and decreased bone density. The etiology of zinc deficiency in SCD is multifactorial, including inadequate dietary intake, increased requirements due to escalations in red cell turnover and elevated urinary losses from renal insufficiency. The investigators hypothesize that bone deficits in individuals with SCD are in part due to zinc deficiency caused by oxidative stress induced hemolysis and elevated bone turnover, and these bone defects can be ameliorated by zinc supplementation.
Studies indicate that zinc improves bone density in thalassemia, a related hemoglobinopathy (Fung, 2013). But thus far, there have not been any randomized prospective studies analyzing the impact of zinc on bone health in individuals with SCD. Although emerging studies have reported that zinc supplementation might improve growth and has the potential for reducing the number and severity of sickle-related painful events, these studies are single center, small and short term. Moreover, there are currently no therapies in SCD focused on bone morbidity, and there is much enthusiasm among individuals with SCD towards participation in a nutritional intervention. A large, multicenter, long term trial of zinc supplementation focused on disease outcomes in SCD is warranted.
In order to determine the optimal tolerated dose of zinc for implementation in a future randomized clinical trial, the investigators have proposed a short term interventional study comparing the effects of two different doses of zinc, 25 vs. 40 mg/day. Subjects will be included if they are between 15 and 40 years of age, have been diagnosed with SCD-SS and are in their steady state of health. The study is a 16-week program, involving 2 baseline blood draws 4 weeks apart, followed by a randomized 12-week zinc intervention. Over the course of the study, the change in measures of bone formation and resorption, will be compared between the usual care period (0 to 4 weeks) and the intervention period (4 to 16 weeks).
- Conditions
- Sickle Cell Disease
- Being tested
- 25 mg/day zinc, 40 mg/day zinc
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
25 mg/day zincDrug
25 mg of zinc as zinc gluconate taken orally once a day
40 mg/day zincDrug
40 mg of zinc as zinc gluconate taken orally once a day
| Study group | Role | What they receive |
|---|---|---|
| Dose 1: Zinc 25 mg/day | Experimental | 25 mg of zinc as zinc gluconate taken orally once a day Receives: Drug: 25 mg/day zinc |
| Dose 2: Zinc 40 mg/day | Experimental | 40 mg of zinc as zinc gluconate taken orally once a day Receives: Drug: 40 mg/day zinc |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarker of Bone Formation (PINP)
Bone formation will be assessed by the change in type I procollagen n-terminal propeptide (PINP) between the usual care period (0-4 weeks) and the intervention period (4-16 weeks). These assays are competitive enzyme immunoassays using microtiter plate formats. Serum will be aliquoted and frozen at -70 until analyzed in batches.
Measured: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
Biomarker of Bone Resorption (CTx)
Bone resorption will be assessed by the change in serum cross-linked C-telopeptide of type I collagen (CTx) during usual care (0 to 4 weeks) and the intervention period (4-16 weeks). These assays are competitive enzyme immunoassays using microtiter plate formats. Serum will be aliquoted and frozen at -70 until analyzed in batches.
Measured: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
Secondary outcomes (2)
Biomarker of Bone Formation (BSAP)
Bone formation will be assessed by the change in bone specific alkaline phosphatase (BSAP) between the usual care period (0-4 weeks) and the intervention period (4-16 weeks). These assays are competitive enzyme immunoassays using microtiter plate formats. Serum will be aliquoted and frozen at -70 until analyzed in batches.
Measured: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
Biomarker of Bone Resorption (TRAP 5b)
Bone resorption will be assessed by the change in tartrate resistant acid phosphatase (TRAP 5b) during usual care (0 to 4 weeks) and the intervention period (4-16 weeks). These assays are competitive enzyme immunoassays using microtiter plate formats. Serum will be aliquoted and frozen at -70 until analyzed in batches.
Measured: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2024
- Study start14 Feb 2026
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a delayed start parallel design where all subjects will have a usual care period, 2 baseline samples 4 weeks apart, followed by a 12 week zinc intervention, with samples at 8 and 12 weeks.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Philadelphia, University of Pennsylvania, Children's Hospital Medical Center, Cincinnati, American Society of Hematology, Baylor College of Medicine, Thomas Jefferson University, Duke University
- Responsible party
- Sponsor
- Investigators
- Ellen Fung, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06260891
- Sponsor's protocol ID
- ZnSCD
- Acronym
- ZnSCD
- Status last verified
- Mar 2026
- First submitted
- 7 Feb 2024
- Last updated
- 13 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data sharing available upon request after the completion of the trial
Publications
Fung EB, Kwiatkowski JL, Huang JN, Gildengorin G, King JC, Vichinsky EP. Zinc supplementation improves bone density in patients with thalassemia: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2013 Oct;98(4):960-71. doi: 10.3945/ajcn.112.049221. Epub 2013 Aug 14.
PubMed 23945720
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zinc Supplementation in Sickle Cell Disease: A Precursor to the Think Zinc for Bones Trial
- ClinicalTrials.gov ID
- NCT06260891
- Acronym / sponsor ID
- ZnSCD / ZnSCD
- Conditions
- Sickle Cell Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Children's Hospital of Philadelphia, University of Pennsylvania, Children's Hospital Medical Center, Cincinnati, American Society of Hematology, Baylor College of Medicine, Thomas Jefferson University, Duke University
- Study start
- 14 Feb 2026 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 15 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this short term prospective Phase II study is to compare the effects of two alternate daily doses of zinc (25 and 40 mg/day) in 34 randomly assigned homozygous Sickle Cell Disease (SCD-SS) patients aged 15-40 years old. The main question it aims to answer is: Which biomarkers are most responsive to zinc supplementation, and what is the maximum tolerated zinc dose that induces the desired changes in biomarkers of bone turnover? Participants will be recruited from 6 American Society Hematology Research Collaborative SCD Centers. Eligible SCD subjects will be invited to participate in the 16-week study, involving 2 baseline blood draws 4 weeks apart, followed by a 12-week zinc intervention. The findings from this study will be used to determine the dosage of zinc to be used in a larger, future study on the long term impact of zinc supplementation on bone health in SCD-SS.
Detailed description
The investigators propose a two-arm, double-blinded, Phase II study comparing the effects of two different daily doses of zinc (25 and 40 mg/day) in 34 patients with SCD-SS aged 15-40 years old, randomly assigned to either group. The aim of the study is to determine the maximum tolerated zinc dose that induces desired changes in rates of bone formation and resorption. The findings from this study will function as preliminary data for a future randomized clinical trial and provide a novel characterization of bone marker response to short term zinc supplementation in SCD that has not previously been described in the literature.
SCD is the most prevalent heritable disorder affecting red blood cells worldwide. It is an autosomal recessive genetic condition inherited at birth when a child receives two genes, one from each parent, coding for abnormal hemoglobin. The defective hemoglobin proteins characteristic of SCD give rise to sickle-shaped red blood cells causing serious health complications, including early onset bone morbidity. Over half of young adults with SCD have osteoporosis and are at increased risk for fracture.
Zinc, an essential trace mineral, is crucial for red cell stability, growth and bone metabolism. Zinc deficiency is reported frequently in patients with SCD and has been related to poor growth, increased vaso-occlusive crises and decreased bone density. The etiology of zinc deficiency in SCD is multifactorial, including inadequate dietary intake, increased requirements due to escalations in red cell turnover and elevated urinary losses from renal insufficiency. The investigators hypothesize that bone deficits in individuals with SCD are in part due to zinc deficiency caused by oxidative stress induced hemolysis and elevated bone turnover, and these bone defects can be ameliorated by zinc supplementation.
Studies indicate that zinc improves bone density in thalassemia, a related hemoglobinopathy (Fung, 2013). But thus far, there have not been any randomized prospective studies analyzing the impact of zinc on bone health in individuals with SCD. Although emerging studies have reported that zinc supplementation might improve growth and has the potential for reducing the number and severity of sickle-related painful events, these studies are single center, small and short term. Moreover, there are currently no therapies in SCD focused on bone morbidity, and there is much enthusiasm among individuals with SCD towards participation in a nutritional intervention. A large, multicenter, long term trial of zinc supplementation focused on disease outcomes in SCD is warranted.
In order to determine the optimal tolerated dose of zinc for implementation in a future randomized clinical trial, the investigators have proposed a short term interventional study comparing the effects of two different doses of zinc, 25 vs. 40 mg/day. Subjects will be included if they are between 15 and 40 years of age, have been diagnosed with SCD-SS and are in their steady state of health. The study is a 16-week program, involving 2 baseline blood draws 4 weeks apart, followed by a randomized 12-week zinc intervention. Over the course of the study, the change in measures of bone formation and resorption, will be compared between the usual care period (0 to 4 weeks) and the intervention period (4 to 16 weeks).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a delayed start parallel design where all subjects will have a usual care period, 2 baseline samples 4 weeks apart, followed by a 12 week zinc intervention, with samples at 8 and 12 weeks.
| Arm | Type | Receives |
|---|---|---|
| Dose 1: Zinc 25 mg/day | Experimental | Drug: 25 mg/day zinc25 mg of zinc as zinc gluconate taken orally once a day |
| Dose 2: Zinc 40 mg/day | Experimental | Drug: 40 mg/day zinc40 mg of zinc as zinc gluconate taken orally once a day |
Who may qualify
- Ages
- 15 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Age: ≥ 15.0 to ≤ 40.0 years
- Diagnosis: SCD-SS or SCD-S Beta zero Thalassemia, in steady state (defined as a minimum of 2 weeks days following pain crisis)
- Male or Female
Key exclusion criteria (6 listed)
- Taking any supplement containing zinc and unable/willing to stop for 3 months prior to study start
- 25-Hydroxy Vitamin D < 20 ng/mL
- On chronic transfusion therapy (defined as >8 Transfusions/year) and iron overloaded (defined as liver iron concentration > 7 mg/g OR average serum ferritin >4000 ug/L)
- Unable swallow pills or take daily supplement as instructed
- Currently participating in another investigational drug trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 25 mg/day zinc25 mg of zinc as zinc gluconate taken orally once a day | Drug | Dose 1: Zinc 25 mg/day |
| 40 mg/day zinc40 mg of zinc as zinc gluconate taken orally once a day | Drug | Dose 2: Zinc 40 mg/day |
Primary outcome
Biomarker of Bone Formation (PINP)
Time frame: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
Bone formation will be assessed by the change in type I procollagen n-terminal propeptide (PINP) between the usual care period (0-4 weeks) and the intervention period (4-16 weeks). These assays are competitive enzyme immunoassays using microtiter plate formats. Serum will be aliquoted and frozen at -70 until analyzed in batches.
Biomarker of Bone Resorption (CTx)
Time frame: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
Bone resorption will be assessed by the change in serum cross-linked C-telopeptide of type I collagen (CTx) during usual care (0 to 4 weeks) and the intervention period (4-16 weeks). These assays are competitive enzyme immunoassays using microtiter plate formats. Serum will be aliquoted and frozen at -70 until analyzed in batches.
2 secondary outcomes
Biomarker of Bone Formation (BSAP)
Time frame: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
Biomarker of Bone Resorption (TRAP 5b)
Time frame: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
- Background: PubMed 23945720Fung EB, Kwiatkowski JL, Huang JN, Gildengorin G, King JC, Vichinsky EP. Zinc supplementation improves bone density in patients with thalassemia: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2013 Oct;98(4):960-71. doi: 10.3945/ajcn.112.049221. Epub 2013 Aug 14.
- Individual participant dataSharing planned: Yes. Data sharing available upon request after the completion of the trial
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ellen Fung, PhD principal investigator
University of California, San Francisco
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 25 mg/day zinc and 40 mg/day zinc in people with Sickle Cell Disease, run by University of California, San Francisco at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Beth Anne Martin (480-793-2162, beth.martin@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarker of Bone Formation (PINP) (time frame: Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06260891, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2026.