Crohn's DiseasePhase 1NCT01046773
Vitamin D Supplementation as Non-toxic Immunomodulation in Children With Crohn's Disease
A Phase 1 study testing Cholecalciferol in people with Crohn's Disease and Vitamin D Deficiency, run by University of California, Los Angeles at 1 site in United States.
Trial summary
IBD is caused by an abnormal immune response to the gut bacteria in people who are genetically predisposed. There has been a huge increase in the number of people diagnosed with IBD since World War II, likely due to changes in our environment. Read more about this study
- Who is it for?
- Ages 8 to 18 years
- Conditions the study is for
- Crohn's Disease, Vitamin D Deficiency
- What is being tested?
- Cholecalciferol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to May 2017
- Phase
- Phase 1
- 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 8 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Clinical diagnosis of mild to moderate Crohn's disease
- 8 to 18 years old, inclusive
Who cannot join
- Children less than 8 years or greater than 18 years at the time of study screening
- Patients with a documented history of hypercalcemia, renal insufficiency, or nephrolithiasis
- Patients taking cholestyramine
- Patients who have a GI tract in discontinuity (ostomy)
- Patients who have serum 25-OH vitamin D levels of >50 ng/mL at the time of study screening
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Los Angeles
Los Angeles, California, 90095
About this study
IBD is caused by an abnormal immune response to the gut bacteria in people who are genetically predisposed. There has been a huge increase in the number of people diagnosed with IBD since World War II, likely due to changes in our environment. It is possible that the abundance of vitamin D in the body may be one of those environmental factors that the investigators can control to make patients with IBD better.
Vitamin D acts on cells of the immune system and causes many effects, including the production of a "natural antibiotic" called cathelicidin. The investigators know that when people are supplemented with vitamin D, levels of cathelicidin produced by these immune cells increase. By supplementing children with Crohn's disease with vitamin D, the investigators may be able to alter their immune system "naturally," making their disease better. A consensus of vitamin D experts believes that vitamin D levels need to reach a level of 40-70 ng/mL in the blood in order to have effects on the immune system. Raising vitamin D levels to this range is one of the goals in the current study.
Read the detailed description
Vitamin D is an important nutrient controlling the health and development of our bones. Many patients with inflammatory bowel disease (IBD) are deficient in levels of vitamin D in their bodies. This is probably because vitamin D is lost from inflamed intestinal tissue into the stools. But while much attention has been given to studying the impact of vitamin D deficiency on the bone status of patients with IBD, our understanding of how vitamin D deficiency might affect the immune system in these patients is relatively poor.
The investigators intend to study vitamin D supplementation in children with Crohn's disease, ages 8 to 18 years. At the time of enrollment, the investigators will gather data on disease activity using both a simple history and physical exam, as well as blood and stool tests. In addition, the investigators will measure the levels of cathelicidin produced by the immune cells in their blood. The investigators will then supplement 20 children with vitamin D for a total of 6 months. During the study, patients will be seen every two months, where the investigators will monitor their vitamin D levels as well as perform rigorous safety monitoring for toxicity using blood and urine tests.
And at study conclusion, the investigators will again judge their disease severity and check their vitamin D levels in addition to tests of cathelicidin levels. The investigators believe that at study conclusion, the investigators will have achieved several important objectives. First, as a public health benefit, the investigators will show that large doses of supplemental vitamin D are safe in children and provide more benefit with less risk. Our patients will achieve those levels of vitamin D agreed by expert opinion that are required to cause effects on the immune system, and the investigators will see an increase in the amount of cathelicidin produced by their immune cells. As an added piece of information, the investigators would like to determine if there are any improvements in disease activity in patients supplemented with vitamin D.
- Conditions
- Crohn's Disease, Vitamin D Deficiency
- Being tested
- Cholecalciferol
- Keywords
- Children, Crohn's disease, Vitamin D
- Medical subject headings
- Crohn Disease, Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CholecalciferolDrug
Children less than 35 kg will receive 2,000 IU oral cholecalciferol daily for 6 months.
CholecalciferolDrug
Children 35 kg or greater will receive 4,000 IU oral cholecalciferol daily for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Children with Crohn's disease less than 35 kg | Active comparator | These are children ages 8 to 18 years inclusive, with mild to moderately active Crohn's disease. Receives: Drug: Cholecalciferol |
| Children with Crohn's disease 35 kg or greater | Active comparator | These are children ages 8 to 18 years inclusive, with mild to moderately active Crohn's disease. Receives: Drug: Cholecalciferol |
What is being measured
The primary outcome is the main question the study is designed to answer.
The investigators aim to achieve patient target serum levels of 25-hydroxy vitamin D between 40-60 ng/mL after 6 months of supplementation
Measured: 6 months
The investigators aim to determine the association between vitamin D supplementation and cathelicidin production.
Measured: 6 months
Secondary outcomes (1)
Detect changes in Crohn's disease activity: clinically, biochemically, and by surrogate markers.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2010 (estimated)
- Study startJan 2010
- Primary completionMay 2017
- Study completionMay 2017
Why it stopped: Low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- The Broad Foundation
- Responsible party
- Sponsor
- Investigators
- David Ziring, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01046773
- Sponsor's protocol ID
- IBD-0285
- Status last verified
- Feb 2018
- First submitted
- 11 Jan 2010
- Last updated
- 7 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in gastrointestinal and liver disease. Curr Opin Gastroenterol. 2008 Mar;24(2):176-83. doi: 10.1097/MOG.0b013e3282f4d2f3.
PubMed 18301268Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008 Dec;29(6):361-8. doi: 10.1016/j.mam.2008.08.008. Epub 2008 Sep 2.
PubMed 18801384Lo CW, Paris PW, Clemens TL, Nolan J, Holick MF. Vitamin D absorption in healthy subjects and in patients with intestinal malabsorption syndromes. Am J Clin Nutr. 1985 Oct;42(4):644-9. doi: 10.1093/ajcn/42.4.644.
PubMed 4050723Vogelsang H, Schofl R, Tillinger W, Ferenci P, Gangl A. 25-hydroxyvitamin D absorption in patients with Crohn's disease and with pancreatic insufficiency. Wien Klin Wochenschr. 1997 Sep 19;109(17):678-82.
PubMed 9331957Leichtmann GA, Bengoa JM, Bolt MJ, Sitrin MD. Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn's disease and intestinal resection. Am J Clin Nutr. 1991 Sep;54(3):548-52. doi: 10.1093/ajcn/54.3.548.
PubMed 1652198Liu N, Nguyen L, Chun RF, Lagishetty V, Ren S, Wu S, Hollis B, DeLuca HF, Adams JS, Hewison M. Altered endocrine and autocrine metabolism of vitamin D in a mouse model of gastrointestinal inflammation. Endocrinology. 2008 Oct;149(10):4799-808. doi: 10.1210/en.2008-0060. Epub 2008 Jun 5.
PubMed 18535110Schauber J, Rieger D, Weiler F, Wehkamp J, Eck M, Fellermann K, Scheppach W, Gallo RL, Stange EF. Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2006 Jun;18(6):615-21. doi: 10.1097/00042737-200606000-00007.
PubMed 16702850Tai EK, Wu WK, Wong HP, Lam EK, Yu L, Cho CH. A new role for cathelicidin in ulcerative colitis in mice. Exp Biol Med (Maywood). 2007 Jun;232(6):799-808.
PubMed 17526772Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, Davidson RN, Sorensen OE, Kampmann B, Griffiths CJ, Wilkinson RJ. IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007 Jun 1;178(11):7190-8. doi: 10.4049/jimmunol.178.11.7190.
PubMed 17513768Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT. A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol. 2003 Dec;17(12):2386-92. doi: 10.1210/me.2003-0281. Epub 2003 Sep 18.
PubMed 14500760Simmons JD, Mullighan C, Welsh KI, Jewell DP. Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility. Gut. 2000 Aug;47(2):211-4. doi: 10.1136/gut.47.2.211.
PubMed 10896912Heaney RP. Lessons for nutritional science from vitamin D. Am J Clin Nutr. 1999 May;69(5):825-6. doi: 10.1093/ajcn/69.5.825. No abstract available.
PubMed 10232617Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56. doi: 10.1093/ajcn/69.5.842.
PubMed 10232622Maalouf J, Nabulsi M, Vieth R, Kimball S, El-Rassi R, Mahfoud Z, El-Hajj Fuleihan G. Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children. J Clin Endocrinol Metab. 2008 Jul;93(7):2693-701. doi: 10.1210/jc.2007-2530. Epub 2008 Apr 29.
PubMed 18445674Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, Borregaard N, Modlin RL, Hewison M. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol. 2009 Apr 1;182(7):4289-95. doi: 10.4049/jimmunol.0803736.
PubMed 19299728
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D Supplementation as Non-toxic Immunomodulation in Children With Crohn's Disease
- ClinicalTrials.gov ID
- NCT01046773
- Acronym / sponsor ID
- IBD-0285
- Conditions
- Crohn's Disease, Vitamin D Deficiency
- Keywords
- Children, Crohn's disease, Vitamin D
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- The Broad Foundation
- Study start
- Jan 2010
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 12 Jan 2010 (estimated)
- 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.
IBD is caused by an abnormal immune response to the gut bacteria in people who are genetically predisposed. There has been a huge increase in the number of people diagnosed with IBD since World War II, likely due to changes in our environment. It is possible that the abundance of vitamin D in the body may be one of those environmental factors that the investigators can control to make patients with IBD better.
Vitamin D acts on cells of the immune system and causes many effects, including the production of a "natural antibiotic" called cathelicidin. The investigators know that when people are supplemented with vitamin D, levels of cathelicidin produced by these immune cells increase. By supplementing children with Crohn's disease with vitamin D, the investigators may be able to alter their immune system "naturally," making their disease better. A consensus of vitamin D experts believes that vitamin D levels need to reach a level of 40-70 ng/mL in the blood in order to have effects on the immune system. Raising vitamin D levels to this range is one of the goals in the current study.
Detailed description
Vitamin D is an important nutrient controlling the health and development of our bones. Many patients with inflammatory bowel disease (IBD) are deficient in levels of vitamin D in their bodies. This is probably because vitamin D is lost from inflamed intestinal tissue into the stools. But while much attention has been given to studying the impact of vitamin D deficiency on the bone status of patients with IBD, our understanding of how vitamin D deficiency might affect the immune system in these patients is relatively poor.
The investigators intend to study vitamin D supplementation in children with Crohn's disease, ages 8 to 18 years. At the time of enrollment, the investigators will gather data on disease activity using both a simple history and physical exam, as well as blood and stool tests. In addition, the investigators will measure the levels of cathelicidin produced by the immune cells in their blood. The investigators will then supplement 20 children with vitamin D for a total of 6 months. During the study, patients will be seen every two months, where the investigators will monitor their vitamin D levels as well as perform rigorous safety monitoring for toxicity using blood and urine tests.
And at study conclusion, the investigators will again judge their disease severity and check their vitamin D levels in addition to tests of cathelicidin levels. The investigators believe that at study conclusion, the investigators will have achieved several important objectives. First, as a public health benefit, the investigators will show that large doses of supplemental vitamin D are safe in children and provide more benefit with less risk. Our patients will achieve those levels of vitamin D agreed by expert opinion that are required to cause effects on the immune system, and the investigators will see an increase in the amount of cathelicidin produced by their immune cells. As an added piece of information, the investigators would like to determine if there are any improvements in disease activity in patients supplemented with vitamin D.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Children with Crohn's disease less than 35 kg | Active comparator | Drug: CholecalciferolThese are children ages 8 to 18 years inclusive, with mild to moderately active Crohn's disease. |
| Children with Crohn's disease 35 kg or greater | Active comparator | Drug: CholecalciferolThese are children ages 8 to 18 years inclusive, with mild to moderately active Crohn's disease. |
Who may qualify
- Ages
- 8 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Clinical diagnosis of mild to moderate Crohn's disease
- 8 to 18 years old, inclusive
Key exclusion criteria (5 listed)
- Children less than 8 years or greater than 18 years at the time of study screening
- Patients with a documented history of hypercalcemia, renal insufficiency, or nephrolithiasis
- Patients taking cholestyramine
- Patients who have a GI tract in discontinuity (ostomy)
- Patients who have serum 25-OH vitamin D levels of >50 ng/mL at the time of study screening
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 |
|---|---|---|
| CholecalciferolChildren less than 35 kg will receive 2,000 IU oral cholecalciferol daily for 6 months. | Drug | Children with Crohn's disease less than 35 kg |
| CholecalciferolChildren 35 kg or greater will receive 4,000 IU oral cholecalciferol daily for 6 months. | Drug | Children with Crohn's disease 35 kg or greater |
Primary outcome
The investigators aim to achieve patient target serum levels of 25-hydroxy vitamin D between 40-60 ng/mL after 6 months of supplementation
Time frame: 6 months
The investigators aim to determine the association between vitamin D supplementation and cathelicidin production.
Time frame: 6 months
1 secondary outcome
Detect changes in Crohn's disease activity: clinically, biochemically, and by surrogate markers.
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Low enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Background: PubMed 18301268Pappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in gastrointestinal and liver disease. Curr Opin Gastroenterol. 2008 Mar;24(2):176-83. doi: 10.1097/MOG.0b013e3282f4d2f3.
- Background: PubMed 18801384Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008 Dec;29(6):361-8. doi: 10.1016/j.mam.2008.08.008. Epub 2008 Sep 2.
- Background: PubMed 4050723Lo CW, Paris PW, Clemens TL, Nolan J, Holick MF. Vitamin D absorption in healthy subjects and in patients with intestinal malabsorption syndromes. Am J Clin Nutr. 1985 Oct;42(4):644-9. doi: 10.1093/ajcn/42.4.644.
- Background: PubMed 9331957Vogelsang H, Schofl R, Tillinger W, Ferenci P, Gangl A. 25-hydroxyvitamin D absorption in patients with Crohn's disease and with pancreatic insufficiency. Wien Klin Wochenschr. 1997 Sep 19;109(17):678-82.
- Background: PubMed 1652198Leichtmann GA, Bengoa JM, Bolt MJ, Sitrin MD. Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn's disease and intestinal resection. Am J Clin Nutr. 1991 Sep;54(3):548-52. doi: 10.1093/ajcn/54.3.548.
- Background: PubMed 18535110Liu N, Nguyen L, Chun RF, Lagishetty V, Ren S, Wu S, Hollis B, DeLuca HF, Adams JS, Hewison M. Altered endocrine and autocrine metabolism of vitamin D in a mouse model of gastrointestinal inflammation. Endocrinology. 2008 Oct;149(10):4799-808. doi: 10.1210/en.2008-0060. Epub 2008 Jun 5.
- Background: PubMed 16702850Schauber J, Rieger D, Weiler F, Wehkamp J, Eck M, Fellermann K, Scheppach W, Gallo RL, Stange EF. Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2006 Jun;18(6):615-21. doi: 10.1097/00042737-200606000-00007.
- Background: PubMed 17526772Tai EK, Wu WK, Wong HP, Lam EK, Yu L, Cho CH. A new role for cathelicidin in ulcerative colitis in mice. Exp Biol Med (Maywood). 2007 Jun;232(6):799-808.
- Background: PubMed 17513768Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, Davidson RN, Sorensen OE, Kampmann B, Griffiths CJ, Wilkinson RJ. IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007 Jun 1;178(11):7190-8. doi: 10.4049/jimmunol.178.11.7190.
- Background: PubMed 14500760Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT. A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol. 2003 Dec;17(12):2386-92. doi: 10.1210/me.2003-0281. Epub 2003 Sep 18.
- Background: PubMed 10896912Simmons JD, Mullighan C, Welsh KI, Jewell DP. Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility. Gut. 2000 Aug;47(2):211-4. doi: 10.1136/gut.47.2.211.
- Background: PubMed 10232617Heaney RP. Lessons for nutritional science from vitamin D. Am J Clin Nutr. 1999 May;69(5):825-6. doi: 10.1093/ajcn/69.5.825. No abstract available.
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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.
David Ziring, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cholecalciferol in people with Crohn's Disease and Vitamin D Deficiency, run by University of California, Los Angeles 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 2 inclusion and 5 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: stopped early, as of the sponsor's last update on 7 Feb 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The investigators aim to achieve patient target serum levels of 25-hydroxy vitamin D between 40-60 ng/mL after 6 months of supplementation (time frame: 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 NCT01046773, which also lists 16 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 7 Feb 2018.