Folic Acid in Pediatric Inflammatory Bowel Disease

NCT ID: NCT03860012

Last Updated: 2019-03-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-11
• Study Completion Date: 2020-05-01

Brief Summary

Inflammatory bowel disease often requires immunomodulators, such as methotrexate, to maintain disease remission. This medication is administered as one dose weekly. Methotrexate can cause folic acid deficiency, so the current recommendation is to give daily folic acid supplementation while on methotrexate. Standard of care is to administer folic acid supplements daily. Patient compliance with daily folic acid is often suboptimal. The rationale is that weekly folic acid supplementation is as efficacious as daily dosing, and less frequent dosing likely will help improve patient compliance. The optimal dosing schedule of folate supplementation in relation to methotrexate is not known and there are not many research studies that have studied changing dosing of folate supplementation. One particular research study examined the effect of different dosing of folic acid supplements in patients with rheumatoid arthritis taking methotrexate. The study showed that folic acid at two different doses per week (5 mg low dose vs 27.5 mg high dose) did not effect the efficacy of methotrexate therapy, and patients who were on either folic acid supplementation had lower toxicity scores compared to patients not on folic acid supplementation. This study shows that folic acid dosed once per week can be useful in preventing methotrexate toxicity for rheumatoid arthritis patients. There were no studies that could be found that have studied this correlation for pediatric inflammatory bowel disease. Based on this current study, once weekly dosing of folic acid in IBD patients on methotrexate has the potential to be as efficacious as daily dosing.

Detailed Description

The purpose of this study is to evaluate the efficacy of once weekly supplemental folic acid dosing compared to daily dosing in patients with inflammatory bowel disease (IBD) on methotrexate.

The study population is pediatric patients (ages 2-21) with inflammatory bowel disease on methotrexate who are receiving supplemental folic acid. The current standard of care is to administer folic acid supplements on a daily basis.

This will be a prospective study involving pediatric IBD patients on methotrexate. Each patient's baseline folate levels and other routine labs at enrollment (time zero) will function as their control at the conclusion of the study.

Doses will be standardized prior to study initiation. All patients will receive 800mcg of supplemental folic acid per week. IBD patients are typically evaluated and have lab draws every 6 months. For our study, labs will be obtained as routine labs (CBC, CMP) and a baseline folate level at the time of enrollment. Once these labs are obtained, patients with normal folate levels will qualify for inclusion in the study. They will be started on once weekly folate dosing. During the course of the study, if patients develop low folate levels, they will be removed from the study and placed back on daily doses of folate.

Conditions

Inflammatory Bowel Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Folic Acid 800 mcg once weekly

Patients on daily folic acid with a normal baseline folate level will be switched to once weekly dosing.

Group Type: EXPERIMENTAL

Folic Acid

Intervention Type: DRUG

Patients on daily folic acid with a normal baseline folate level will be switched to once weekly dosing.

Interventions

Folic Acid

Patients on daily folic acid with a normal baseline folate level will be switched to once weekly dosing.

Intervention Type: DRUG

Other Intervention Names

Folate

Eligibility Criteria

Inclusion Criteria

1. inflammatory bowel disease

2. on methotrexate at appropriate dosing

3. normal folate levels at onset of study

4. treatment with folic acid

5. ages 2-21 years

Exclusion Criteria

1. abnormal folate levels

2. age > 21 or less than 2

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Le Bonheur Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tsega A Temtem, MD

Role: PRINCIPAL_INVESTIGATOR

UTHSC

Locations

LeBonheur Children's Hospital

Memphis, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Tsega A Temtem, MD

Role: CONTACT

ttemtem@uthsc.edu

901-287-7337

John R Whitworth, MD

Role: CONTACT

jwhitwor@uthsc.edu

901-287-7337

Facility Contacts

Tsega A Temtem, MD

Role: primary

ttemtem@uthsc.edu

901-287-7489

John R Whitworth, MD

Role: backup

jwhitwor@uthsc.edu

901-287-4017

References

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Reference Type: RESULT

PMID: 24063425 (View on PubMed)

Bermejo F, Algaba A, Guerra I, Gisbert JP. Response to letter: folate deficiency in Crohn's disease. Scand J Gastroenterol. 2014 Feb;49(2):255-6. doi: 10.3109/00365521.2013.869829. Epub 2013 Dec 16.

Reference Type: RESULT

PMID: 24328943 (View on PubMed)

Dhir V, Sandhu A, Kaur J, Pinto B, Kumar P, Kaur P, Gupta N, Sood A, Sharma A, Sharma S. Comparison of two different folic acid doses with methotrexate--a randomized controlled trial (FOLVARI Study). Arthritis Res Ther. 2015 Jun 11;17(1):156. doi: 10.1186/s13075-015-0668-4.

Reference Type: RESULT

PMID: 26063325 (View on PubMed)

Dupont-Lucas C, Grandjean-Blanchet C, Leduc B, Tripcovici M, Larocque C, Gervais F, Jantchou P, Amre D, Deslandres C. Prevalence and Risk Factors for Symptoms of Methotrexate Intolerance in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017 Feb;23(2):298-303. doi: 10.1097/MIB.0000000000001014.

Reference Type: RESULT

PMID: 28107279 (View on PubMed)

Heyman MB, Garnett EA, Shaikh N, Huen K, Jose FA, Harmatz P, Winter HS, Baldassano RN, Cohen SA, Gold BD, Kirschner BS, Ferry GD, Stege E, Holland N. Folate concentrations in pediatric patients with newly diagnosed inflammatory bowel disease. Am J Clin Nutr. 2009 Feb;89(2):545-50. doi: 10.3945/ajcn.2008.26576. Epub 2008 Dec 30.

Reference Type: RESULT

PMID: 19116333 (View on PubMed)

Kaskel FJ, Bamgbola OF. Validation of a composite scoring scheme in the diagnosis of folate deficiency in a pediatric and adolescent dialysis cohort. J Ren Nutr. 2008 Sep;18(5):430-9. doi: 10.1053/j.jrn.2008.05.009.

Reference Type: RESULT

PMID: 18721738 (View on PubMed)

Pan Y, Liu Y, Guo H, Jabir MS, Liu X, Cui W, Li D. Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis. Nutrients. 2017 Apr 13;9(4):382. doi: 10.3390/nu9040382.

Reference Type: RESULT

PMID: 28406440 (View on PubMed)

Park JA, Shin HY. Influence of genetic polymorphisms in the folate pathway on toxicity after high-dose methotrexate treatment in pediatric osteosarcoma. Blood Res. 2016 Mar;51(1):50-7. doi: 10.5045/br.2016.51.1.50. Epub 2016 Mar 25.

Reference Type: RESULT

PMID: 27104192 (View on PubMed)

Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014 May;44(5):480-8. doi: 10.3109/00498254.2013.845705. Epub 2014 Feb 4.

Reference Type: RESULT

PMID: 24494987 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

Folic acid in Peds IBD

Identifier Type: -

Identifier Source: org_study_id