Zinc Supplementation in Sickle Cell Disease (ZnSCD)

March 9, 2024 updated by: University of California, San Francisco

Zinc Supplementation in Sickle Cell Disease: A Precursor to the 'Think Zinc for Bones' Trial

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 15-35 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 7 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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 15-35 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.

Recent publications 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 maximum 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 35 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 Type

Interventional

Enrollment (Estimated)

34

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age: ≥ 15.0 to ≤ 35.0 years
  • Diagnosis: SCD-SS, in steady state (defined as a minimum of 10 days following pain crisis)
  • Male or Female (n=17 of each) stratified by age group (15-25 ; 25-35 years)

Exclusion Criteria:

  • Taking zinc supplements and unable/willing to stop for 3 months prior to study start
  • On chronic transfusion therapy (defined as >8 Transfusions/year)
  • Unable swallow pills or take daily supplement as instructed
  • Renal dysfunction (defined as creatinine > 1.5 mg/dL or estimated glomerular filtration rate < 60)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose 1: Zinc 25 mg/day
25 mg of zinc as zinc gluconate taken orally once a day
Drug: 25 mg/day zinc
25 mg of zinc as zinc gluconate taken orally once a day
Experimental: Dose 2: Zinc 40 mg/day
40 mg of zinc as zinc gluconate taken orally once a day
Drug: 40 mg/day zinc
40 mg of zinc as zinc gluconate taken orally once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)
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.
Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
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)
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.
Total 16 weeks divided into: Usual Care (0 to 4 weeks) vs. Intervention Period (4 to 16 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Johns Hopkins University
Baylor College of Medicine
Children's Hospital of Philadelphia
University of Pennsylvania
Children's Hospital Medical Center, Cincinnati
Children's National Research Institute
Newark Beth Israel Medical Center
American Society Hematology, Research Collaborative

Investigators

  • Principal Investigator: Ellen Fung, PhD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2025

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

February 7, 2024

First Submitted That Met QC Criteria

February 7, 2024

First Posted (Actual)

February 15, 2024

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 9, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZnSCD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This project is being submitted for funding. When funded, a plan will be developed for possible data sharing.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sickle Cell Disease

Clinical Trials on 25 mg/day zinc

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Pakistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe