the Effect of Vitamin D in Crohn's Disease

the Effect of Target-oriented Vitamin D Treatment in Refractory Crohn's Disease

To evaluate the efficacy and safety of 12-week goal-directed therapy in the treatment of refractory inflammatory patients, and to initially explore treatment options. Patients with potential risk factors for recurrence after surgery for Crohn's disease and a serum 25(OH)D concentration <75 nmol/L were prescribed oral liquid vitamin D supplementation over 12 weeks using a specific protocol with dose adjusted 4-weekly to aim for a target level of 100-125 nmol/L.

Study Overview

• Status: Unknown
• Conditions: Vitamin D Deficiency; Crohn Disease
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: Vitamin D

Detailed Description

The patients received oral liquid cholecalciferol supplementation (OsteVit DTM, Key Pharmaceuticals, Macquarie Park, NSW, Australia), supplied in 50 mL bottles (5000 units in 1 mL). A target 25(OH)D of 100-125 nmol/L was planned and the dose titrated 4-weekly.

Patients were evaluated at week 0 (screening visit), then 2- weekly until week 12, and at a follow-up visit at week 16. Key study endpoints were change in total 25(OH)D and attainment of level of 100e125 nmol/L. Intestinal inflammation was assessed via clinical disease activity (CDAI), faecal calprotectin (Calprotectin ELISA, Buhlmann, Basel, Switzerland), and circulating inflammatory markers (platelet count, serum albumin and C- reactive protein). Safety was assessed by direct questioning and 24- h urinary calcium excretion . Compliance was checked by dosing diaries completed by patients and measuring remaining cholecalciferol in bottles of the study drug.

Statistical analyses were performed using SPSS v20 (IBM Corporation, 2011) and GraphPad Prism v5.04 (Graphpad software, 2010). Dependent and independent samples t-tests, analysis of variance (ANOVA) and KruskaleWallis tests were used where appropriate. Associations with rise in 25(OH)D were examined by bivariate correlations. A p-value of 0.05 was considered statistically significant.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Lei Zheng, doctor; Phone Number: 86-13705270060; Email: blanch_zll@hotmail.com
• Study Contact Backup: Name: Lei Zheng, doctor; Phone Number: 86-137-5260060; Email: blanch_zll@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical diagnosis of Crohn's Disease
2. Must be able to swallow tablets

3. Have certain factors increase the risk of surgery in CD. include:

   • current smoking
   • fistulizing and stricturing disease behaviour
   • early steroid use (medical need for steroids for treatment of first flare)
   • disease in the end of the small bowel (i.e. ileum)
   • disease in the middle part of the small bowel (i.e. jejunum), and
   • young age at the time of the diagnosis.

Exclusion Criteria:

1. Other serious gastrointestinal diseases
2. pregnancy
3. hypercalcemia
4. hyperparathyroidism
5. chronic kidney disease and cardiovascular disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; The physical properties such as appearance, size, color, dosage form, weight, taste and odor of placebo should be as much as possible as the test drug, but should not contain the Vitamin D (such as tablets containing lactose).	Drug: Placebo oral capsule; the capsule contain nothing; Other Names: Placebo
Experimental: Vitamin D group; Liquid cholecalciferol supplementation (OsteVit DTM, Key Pharmaceuticals, Macquarie Park, NSW, Australia), supplied in 50 mL bottles (5000 units in 1 mL)	Drug: Vitamin D; patients with refractory Crohn disease and a serum 25(OH)D concentration <75 nmol/L were prescribed oral liquid vitamin D supplementation over 12 weeks using a specific protocol with dose adjusted 4-weekly to aim for a target level of 100e125 nmol/L.; Other Names: VD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical disease activity	CDAI score	up to one year
Fecal calprotectin	Calprotectin is a calcium-containing protein derived from neutrophils and macrophages. Its expression is tissue or cell specific and can be used as a marker for activation of acute inflammatory cells.	up to one year
C-reactive protein	circulating inflammatory markers	up to one year
Discomportant complaint	Incidence of Treatment Adverse Events	up to one year
24-hour urinary calcium	Determination of calcium in urine for 24 hours	up to one year

Collaborators and Investigators

• Sponsor: Nanjing University School of Medicine
• Collaborators: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• Investigators: Study Chair: Yousheng Li, Doctor, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Publications and helpful links

General Publications

• Garg M, Rosella O, Rosella G, Wu Y, Lubel JS, Gibson PR. Evaluation of a 12-week targeted vitamin D supplementation regimen in patients with active inflammatory bowel disease. Clin Nutr. 2018 Aug;37(4):1375-1382. doi: 10.1016/j.clnu.2017.06.011. Epub 2017 Jun 15.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): October 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: October 17, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 21, 2019

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Vitamin D; recurrence; Crohn Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Nutrition Disorders; Gastroenteritis; Intestinal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Inflammatory Bowel Diseases; Vitamin D Deficiency; Crohn Disease; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: SJUSM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No