Inflammatory Bowel DiseasesPhase 4NCT03860012
Folic Acid in Pediatric Inflammatory Bowel Disease
A Phase 4 study testing Folic Acid in people with Inflammatory Bowel Diseases, run by Le Bonheur Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Inflammatory Bowel Diseases
- What is being tested?
- Folic Acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Sep 2018to 1 May 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- inflammatory bowel disease
- on methotrexate at appropriate dosing
- normal folate levels at onset of study
- treatment with folic acid
- ages 2-21 years
Who cannot join
- abnormal folate levels
- age > 21 or less than 2
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
LeBonheur Children's Hospital
Memphis, Tennessee, 38103
Tsega A Temtem, MD, 901-287-7489, ttemtem@uthsc.edu
John R Whitworth, MD, 901-287-4017, jwhitwor@uthsc.edu
About this study
Official title: Evaluating the Efficacy of Weekly Folic Acid in Pediatric Inflammatory Bowel Disease Patients on Methotrexate
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.
Read the 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
- Being tested
- Folic Acid
- Keywords
- methotrexate, folic, acid
- Medical subject headings
- Inflammatory Bowel Diseases, Heartburn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folic AcidDrug
Also called Folate
Patients on daily folic acid with a normal baseline folate level will be switched to once weekly dosing.
| Study group | Role | What they receive |
|---|---|---|
| Folic Acid 800 mcg once weekly | Experimental | Patients on daily folic acid with a normal baseline folate level will be switched to once weekly dosing. Receives: Drug: Folic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Folate level
Evaluation of Folate level
Measured: at 6 months
Evaluation of Folate level
Evaluation of Folate level
Measured: at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start11 Sep 2018
- Primary completion31 Dec 2019 (estimated)
- Study completion1 May 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel DiseasesStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All patients will receive 800mcg of supplemental folic acid per week.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Le Bonheur Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tsega A Temtem, MD, Principal investigator, UTHSC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03860012
- Sponsor's protocol ID
- Folic acid in Peds IBD
- Status last verified
- Feb 2019
- First submitted
- 13 Feb 2019
- Last updated
- 1 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bermejo F, Algaba A, Guerra I, Chaparro M, De-La-Poza G, Valer P, Piqueras B, Bermejo A, Garcia-Alonso J, Perez MJ, Gisbert JP. Should we monitor vitamin B12 and folate levels in Crohn's disease patients? Scand J Gastroenterol. 2013 Nov;48(11):1272-7. doi: 10.3109/00365521.2013.836752. Epub 2013 Sep 25.
PubMed 24063425Bermejo 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.
PubMed 24328943Dhir 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.
PubMed 26063325Dupont-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.
PubMed 28107279Heyman 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.
PubMed 19116333Kaskel 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.
PubMed 18721738Pan 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.
PubMed 28406440Park 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.
PubMed 27104192Scaglione 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.
PubMed 24494987
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Efficacy of Weekly Folic Acid in Pediatric Inflammatory Bowel Disease Patients on Methotrexate
- ClinicalTrials.gov ID
- NCT03860012
- Acronym / sponsor ID
- Folic acid in Peds IBD
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- methotrexate, folic, acid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Le Bonheur Children's HospitalUniversity, hospital or other
- Study start
- 11 Sep 2018 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 1 May 2020 (estimated)
- First posted
- 1 Mar 2019 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All patients will receive 800mcg of supplemental folic acid per week.
| Arm | Type | Receives |
|---|---|---|
| Folic Acid 800 mcg once weekly | Experimental | Drug: Folic AcidPatients on daily folic acid with a normal baseline folate level will be switched to once weekly dosing. |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- inflammatory bowel disease
- on methotrexate at appropriate dosing
- normal folate levels at onset of study
- treatment with folic acid
- ages 2-21 years
Key exclusion criteria (2 listed)
- abnormal folate levels
- age > 21 or less than 2
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 |
|---|---|---|
| Folic AcidAlso: FolatePatients on daily folic acid with a normal baseline folate level will be switched to once weekly dosing. | Drug | Folic Acid 800 mcg once weekly |
Primary outcome
Evaluation of Folate level
Time frame: at 6 months
Evaluation of Folate level
Evaluation of Folate level
Time frame: at 12 months
Evaluation of Folate level
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2019.
- Results publication: PubMed 24063425Bermejo F, Algaba A, Guerra I, Chaparro M, De-La-Poza G, Valer P, Piqueras B, Bermejo A, Garcia-Alonso J, Perez MJ, Gisbert JP. Should we monitor vitamin B12 and folate levels in Crohn's disease patients? Scand J Gastroenterol. 2013 Nov;48(11):1272-7. doi: 10.3109/00365521.2013.836752. Epub 2013 Sep 25.
- Results publication: PubMed 24328943Bermejo 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.
- Results publication: PubMed 26063325Dhir 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.
- Results publication: PubMed 28107279Dupont-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.
- Results publication: PubMed 19116333Heyman 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.
- Results publication: PubMed 18721738Kaskel 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.
- Results publication: PubMed 28406440Pan 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.
- Results publication: PubMed 27104192Park 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.
- Results publication: PubMed 24494987Scaglione 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.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Tsega A Temtem, MD principal investigator
UTHSC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Folic Acid in people with Inflammatory Bowel Diseases, run by Le Bonheur Children's Hospital at 1 site 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 5 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 1 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tsega A Temtem, MD (901-287-7337, ttemtem@uthsc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of Folate level (time frame: at 6 months). 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 NCT03860012, which also lists 9 linked publications.
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 1 Mar 2019.