- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04011345
Folic Acid Supplementation in Children With Sickle Cell Disease
Folic Acid Supplementation in Children With Sickle-Cell Disease: A Randomized Double-Blind Cross-Over Trial
Folic acid supplementation (1mg/d) is the standard recommendation for Canadian children with Sickle cell disease (SCD), even though it can provide up to six times the recommended intake amount for healthy children. There is growing concern that too much folic acid can be detrimental to health as high folate levels and circulating unmetabolized folic acid (UMFA), which occurs in blood with doses of folic acid as low as 0.2mg/d, have been associated with accelerated growth of some pre-cancerous cells, and altered DNA methylation and gene expression.
To inform the efficacy and potential harm of high-dose folic acid supplementation in Canadian children with SCD, a double-blind randomized controlled cross-over trial is proposed. Children with SCD (n=36, aged 2-19 y) will be recruited from BC Children's Hospital and randomized to initially receive 1 mg/d folic acid or a placebo for 12-weeks (wk). After a 12-wk washout period, treatments will be reversed.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Blood samples will be collected at baseline and 12-wk of each treatment period (weeks 12, 24, and 36).
Serum and RBC concentrations of total folate, different folate forms and clinical outcomes will be measured at baseline and after each treatment period. Dietary folate intake will be assessed at baseline.
The objective of this study is to determine efficacy and potential harm of folic acid supplementation, versus no supplementation, in Canadian children with sickle cell disease.
It is hypothesized that: (1) there will be no difference in mean RBC folate concentrations across folic acid and placebo groups after 12-wk, (2) none of the participants will have folate deficiency, and (3) compared to periods of no supplementation, during periods of high-dose folic acid supplementation participants will show no difference in clinical outcomes, but have higher plasma unmetabolized folic acid concentrations.
Significance: There is a need to determine if the current clinical practice of high-dose folic acid supplementation is efficacious, and warranted.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Brock Williams, MSc, RD
- Phone Number: 905-999-3710
- Email: brock.williams@ubc.ca
Study Contact Backup
- Name: Crystal Karakochuk, PhD, RD
- Phone Number: 604-710-8496
- Email: crystal.karakochuk@ubc.ca
Study Locations
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V6H 3N1
- BC Children's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Individuals with SCD aged 2-19 y attending British Columbia Children's Hospital
- Individuals having received routine daily supplementation of folic acid for the prior 12-weeks
Exclusion Criteria:
- Individuals receiving a blood transfusion in the prior 12-weeks
- Individuals allergic to any components of the supplement (cellulose, methylcellulose, magnesium stearate, and/or titanium dioxide)
- Individuals presenting with megaloblastic anemia in the prior 12-weeks
- Individuals with pulmonary, renal and/or cardiac complications (severe or recurrent acute chest syndrome)
- Individuals routinely taking medications known to interfere with B vitamin metabolism (chloramphenicol, methotrexate, metformin, sulfasalazine, phenobarbital, primidone, triamterene, barbiturates)
- Individuals who are currently pregnant, planning to become pregnant in the next 9-months, or currently breastfeeding
- Individuals who have participated in a clinical research trial in the previous 30 days
- Individuals who have donated blood in the previous 30 days
- Individuals with unstable medical conditions or unstable laboratory results.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Folic Acid Supplement [Phase 1]
Phase 1: Folic acid supplement (1 mg per day) for 12 weeks; Phase 2: Wash-out period (no supplement or placebo) for 12 weeks; Phase 3: Placebo for 12 weeks
|
Placebo
1 milligram folic acid
|
Other: Placebo [Phase 1]
Phase 1: Placebo for 12 weeks; Phase 2: Wash-out period (no supplement or placebo) for 12 weeks; Phase 3: Folic acid supplement (1 mg per day) for 12 weeks
|
Placebo
1 milligram folic acid
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Red Blood Cell Folate Concentration
Time Frame: 12 weeks
|
Biochemical folate status marker (nmol/L)
|
12 weeks
|
Red Blood Cell Folate Concentration
Time Frame: 36 weeks
|
Biochemical folate status marker (nmol/L)
|
36 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum Folate Concentration
Time Frame: 12 weeks
|
Biochemical folate status marker (nmol/L)
|
12 weeks
|
Serum Folate Concentration
Time Frame: 36 weeks
|
Biochemical folate status marker (nmol/L)
|
36 weeks
|
Plasma Unmetabolized Folic Acid Concentration
Time Frame: 12 weeks
|
Biochemical folate marker (nmol/L)
|
12 weeks
|
Plasma Unmetabolized Folic Acid Concentration
Time Frame: 36 weeks
|
Biochemical folate marker (nmol/L)
|
36 weeks
|
S-adenosyl-methionine Concentration
Time Frame: 12 weeks
|
Biochemical folate metabolite (µmol/L)
|
12 weeks
|
S-adenosyl-methionine Concentration
Time Frame: 36 weeks
|
Biochemical folate metabolite (µmol/L)
|
36 weeks
|
S-adenosyl-homocysteine Concentration
Time Frame: 12 weeks
|
Biochemical folate metabolite (µmol/L)
|
12 weeks
|
S-adenosyl-homocysteine Concentration
Time Frame: 36 weeks
|
Biochemical folate metabolite (µmol/L)
|
36 weeks
|
Total homocysteine Concentration
Time Frame: 12 weeks
|
Biochemical folate metabolite (µmol/L)
|
12 weeks
|
Total homocysteine Concentration
Time Frame: 36 weeks
|
Biochemical folate metabolite (µmol/L)
|
36 weeks
|
Acute Pain Crises
Time Frame: 12 weeks
|
Participant self-reported occurrence (# of episodes, and severity of episodes)
|
12 weeks
|
Acute Pain Crises
Time Frame: 36 weeks
|
Participant self-reported occurrence (# of episodes, and severity of episodes)
|
36 weeks
|
Megaloblastic anemia
Time Frame: 12 weeks
|
Determined by hemoglobin and Mean Corpuscular Volume (MCV) concentrations below/above age-specific hematological cut-offs
|
12 weeks
|
Megaloblastic anemia
Time Frame: 36 weeks
|
Determined by hemoglobin and Mean Corpuscular Volume (MCV) concentrations below/above age-specific hematological cut-offs
|
36 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Crystal Karakochuk, PhD, RD, University of British Columbia
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H18-02981
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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