Vitamin D Supplementation as Non-toxic Immunomodulation in Children With Crohn's Disease

NCT01046773 | Terminated Phase 1 DMC

• 1 other identifier: IBD-0285
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Crohn's Disease; Vitamin D Deficiency

Keywords

Children; Crohn's disease; Vitamin D

Outcome Measures

Primary Outcomes (2)

• The investigators aim to achieve patient target serum levels of 25-hydroxy vitamin D between 40-60 ng/mL after 6 months of supplementation

  6 months

• The investigators aim to determine the association between vitamin D supplementation and cathelicidin production.

  6 months

Secondary Outcomes (1)

• Detect changes in Crohn's disease activity: clinically, biochemically, and by surrogate markers.

  6 months

Study Arms (2)

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.

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.

Drug: Cholecalciferol

Interventions

Cholecalciferol DRUG

Children less than 35 kg will receive 2,000 IU oral cholecalciferol daily for 6 months.

Children with Crohn's disease less than 35 kg

Eligibility Criteria

• Age: 8 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Clinical diagnosis of mild to moderate Crohn's disease
• to 18 years old, inclusive

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• The Broad Foundation: collaborator

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Related Publications (16)

• 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.

  PMID: 18301268 BACKGROUND

• Holick 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.

  PMID: 18801384 BACKGROUND

• Lo 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.

  PMID: 4050723 BACKGROUND

• Vogelsang 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.

  PMID: 9331957 BACKGROUND

• Leichtmann 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.

  PMID: 1652198 BACKGROUND

• Liu 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.

  PMID: 18535110 BACKGROUND

• Schauber 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.

  PMID: 16702850 BACKGROUND

• Tai 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.

  PMID: 17526772 BACKGROUND

• Martineau 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.

  PMID: 17513768 BACKGROUND

• Froicu 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.

  PMID: 14500760 BACKGROUND

• Simmons 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.

  PMID: 10896912 BACKGROUND

• Heaney 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.

  PMID: 10232617 BACKGROUND

• Vieth 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.

  PMID: 10232622 BACKGROUND

• Maalouf 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.

  PMID: 18445674 BACKGROUND

• Adams 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.

  PMID: 19299728 BACKGROUND

• Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007 Dec;22 Suppl 2:V64-8. doi: 10.1359/jbmr.07s221.

  PMID: 18290725 BACKGROUND

MeSH Terms

Conditions

Crohn Disease; Vitamin D Deficiency

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• David Ziring, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 12, 2010
• Study Start: January 1, 2010
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: February 7, 2018

Record last verified: 2018-02

Locations

US (1)