Vitamin D3 in Pediatric SLE

This study is currently recruiting participants.
Verified January 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborator:
Autoimmunity Centers of Excellence
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01709474
First received: October 16, 2012
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

The primary objective of this study is to compare the impact of 18 weeks of high-dose vitamin D3 supplementation vs. standard-dose vitamin D3 supplementation on immune hyperactivation as measured by the interferon (IFN) signature in a pediatric population diagnosed with systemic lupus erythematosus (SLE) and vitamin D deficiency.


Condition Intervention Phase
Systemic Lupus Erythematosus
Drug: Vitamin D3
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vitamin D3 Effects on Immune Function in Pediatric Systemic Lupus Erythematosus (SLE)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • The change in average IFN module expression level [ Time Frame: baseline to week 18 ] [ Designated as safety issue: No ]
  • The proportion of subjects in each study arm experiencing any adverse event (AE) ≥ Grade 3 [ Time Frame: baseline to 18 weeks ] [ Designated as safety issue: Yes ]
    Adverse event grading based on National Cancer Institute— Common Terminology Criteria for Adverse Events (NCI-CTCAE)


Estimated Enrollment: 78
Study Start Date: June 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Dose Vitamin D3
Subjects randomized to the high-dose arm will receive 6,000 IU per day until the subject's serum 25(OH) level is ≥ 40ng/mL at which point the supplementation dose will be reduced to 4,000 IU/day.
Drug: Vitamin D3
Active Comparator: Low Dose Vitamin D3
400 IU/day of vitamin D3
Drug: Vitamin D3

Detailed Description:

This is a multi-center, phase II, 18-week, two arm, unblinded, mechanistic randomized clinical trial to evaluate the effects of high-dose vitamin D3 supplementation compared with standard-dose supplementation, on immune function, glucose homeostasis, and bone metabolism.

Seventy-eight pediatric subjects with SLE and 25(OH)D levels ≤ 20 ng/mL will be randomized in a 1:1 ratio to receive either standard-dose (400 IU/day) or highdose (6,000 IU/day) vitamin D3 for 18 weeks based upon weight at baseline. Subjects randomized to the high-dose vitamin D3 treatment arm will receive 6,000 IU per day from baseline until the subject's vitamin D levels reach ≥ 40 ng/mL at which point the vitamin D3 dose will be reduced to 4,000 IU per day. Subjects randomized to the high-dose treatment arm weighing < 40 kg will receive supplementation five days per week and all other subjects will receive supplementation seven days a week.

In addition to the baseline, and weeks 6, 12, and 18 visits, subjects randomized to the high-dose treatment arm will return at Weeks 3 and 9 to assess vitamin D toxicity. If a subject in the high-dose arm is found to exhibit evidence of vitamin D toxicity at the week 12 visit, he/she will be asked to return to the site for an additional vitamin D toxicity assessment at week 15. Study personnel will record each subject's interval history, assess adverse events, disease activity, and collect samples for safety and mechanistic assessments.

  Eligibility

Ages Eligible for Study:   5 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent signed by the subject or parent/guardian as appropriate; child assent as appropriate
  • Before the age of 19, met at least 4 of the 11 modified American College of Rheumatology (ACR) 1982 Revised Criteria for the Classification of Systemic Lupus Erythematosus as updated in 1997.
  • Date of SLE diagnosis (as described in Inclusion Criterion 2) at least 24 weeks prior to randomization
  • Serum 25(OH) D < 20 ng/mL at Screening
  • SELENA SLEDAI score > 0 and < 8 at Screening and at Baseline
  • If taking prednisone (or equivalent corticosteroid), the dose must be ≤ 15 mg/day or ≤ 0.5 mg/kg/day, whichever is lower, and stable for at least four weeks prior to randomization. Note, if subjects are taking steroids every other day, divide their dose by 2 to evaluate eligibility.
  • Stable immunosuppressive dose for at least 12 weeks prior to randomization. Immunosuppressive medications allowed include mycophenolate, azathioprine, methotrexate, antimalarial medications (e.g., hydroxychloroquine), cyclosporine A, tacrolimus, IVIG, and abatacept
  • Body weight > 25 kg
  • Able to swallow pills at randomization
  • Males and females with reproductive potential must agree to practice effective measures of birth control

Exclusion Criteria:

  • Any condition or treatment that, in the opinion of the investigator, places the subject at an unacceptable risk as a participant in the trial
  • Current pharmacologic vitamin D2 or D3 intake > 800 IU per day or use of calcitriol at any dose over the past four weeks prior to randomization
  • Cyclophosphamide or IV glucocorticoid exposure within 12 weeks prior to randomization
  • Any BILAG A or B manifestation with the exception of a BILAG B mucocutaneous manifestation at screening, and excluding the renal BILAG criteria (see criterion #5, below)
  • Significant renal insufficiency defined as:

    i. Estimated GFR < 60 mL/min/1.73m2 [95] or estimated GFR < 90 mL/min/1.73m2 with a reduction of the GFR by > 15% from the last measurement. ii. Urine dipstick value of 2+ or higher for protein, unless this is a stable value from the last measurement or, urine protein-creatinine ratio ≥ 50 mg/mmol unless the value represents an improvement of ≥ 25% from the last measurement.

  • Rituximab or belimumab exposure use within 24 weeks prior to randomization
  • The following laboratory parameters at the Screening visit:

    • Platelets < 50,000; WBC < 2,500; ANC < 1,000
    • Hemoglobin < 9 mg/dL
    • ALT, AST, bilirubin > 2x ULN
    • Hypercalcemia (Calcium > ULN)
    • Hypercalciuria (urinary calcium/creatinine ratio > 0.2)
  • Primary hyperparathyroidism (known)
  • History of nephrolithiasis (known)
  • Diabetes mellitus requiring insulin therapy
  • Medications that interfere with vitamin D absorption (refer to Section 5.7, Prohibited Medications, for details)
  • History of vertebral compression fractures (known)
  • Pregnancy (girls ≥ 11 years of age must have a negative urine/serum pregnancy test)
  • A history of non-adherence/non-compliance
  • Other investigational drug and/or treatment during the four weeks or seven half-lives of the other investigational drug prior to the start of study product dosing (Day 0), whichever is the greater length of time to enrollment
  • Current diagnosis of cancer or chronic infection such as Hepatitis B, Hepatitis C, or tuberculosis
  • Treatment with digoxin
  • Flu vaccination within one week prior to randomization
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01709474

Locations
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Ana Cabrera    323-361-5958    ancabrera@chla.usc.edu   
Principal Investigator: Bracha Shaham, MD         
Lucile Packard Children's Hospital Recruiting
Palo Alto, California, United States, 94304
Contact: Elizabeth Merkel    650-736-0644    merkel@stanford.edu   
Principal Investigator: Christy Sandborg, MD         
UCSF School of Medicine Recruiting
San Francisco, California, United States, 94143
Contact: Deborah Carlton    415-502-7685    CarltonD@peds.ucsf.edu   
Principal Investigator: Emily von Scheven, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Erin Thomas    773-880-4360    ethomas@luriechildrens.org   
Principal Investigator: Marisa Klein-Gitelman, MD         
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Becky Puplava    773-702-2879    rpuplava@peds.bsd.uchicago.edu   
Principal Investigator: Karen Onel, MD         
United States, Indiana
Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Andrea Hudgins    317-274-2172    abamford@iu.edu   
Principal Investigator: Peter Chira, MD         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Arisa Kapedani    718-741-2456    akapedan@montefiore.org   
Principal Investigator: Jay Mehta, MD, MS         
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Afshin Zartoshti       az2200@columbia.edu   
Principal Investigator: Lisa Imundo, MD         
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Barbra Murante, MS, RN    585-273-3462    barbra_murante@urmc.rochester.edu   
Principal Investigator: David Siegel, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Janet Wootton, RN-BC RSCN    919-684-2575    janet.wootton@duke.edu   
Principal Investigator: Laura Shanberg, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jenna Tress    267-426-8153    tressj@email.chop.edu   
Principal Investigator: John Burnham, MD         
United States, Texas
Children's Medical Center of Dallas Recruiting
Dallas, Texas, United States, 75235
Contact: Evin Shirley    214-456-9501    evin.shirley@childrens.com   
Principal Investigator: Tracey Wright, MD         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98101
Contact: Gretchen Henstorf, BA, CCRC    206-987-2057      
Principal Investigator: Anne Stevens, MD, PhD         
Sponsors and Collaborators
Autoimmunity Centers of Excellence
Investigators
Study Chair: Jon M Burnham, MD, MSCE University of Pennsylvania
Study Chair: Emily Von Scheven, MD, MAS University of California, San Francisco
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01709474     History of Changes
Other Study ID Numbers: DAIT ALE05
Study First Received: October 16, 2012
Last Updated: January 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on April 16, 2014