Vitamin D3 Treatment in Pediatric Systemic Lupus Erythematosus

This study has been terminated.
(Due to slow enrollment)
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: October 10, 2014
Last verified: October 2014
  Purpose

The primary objective of this study is to evaluate the effects of 18 weeks of high-dose vitamin D3 supplementation compared with standard-dose vitamin D3 supplementation on immune function, glucose homeostasis, and bone metabolism in children with systemic lupus erythematosus (SLE) and serum 25-hydroxyvitamin D [25(OH)D] levels <=20 ng/mL.


Condition Intervention Phase
Systemic Lupus Erythematosus
Drug: High-Dose Vitamin D3
Drug: Standard-Dose Vitamin D3
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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:
  • Change in Average IFN Module Expression Level [ Time Frame: Baseline to Week 18 ] [ Designated as safety issue: No ]
  • Proportion of Subjects by Treatment 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), Version 4.0


Enrollment: 7
Study Start Date: June 2013
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High-Dose Vitamin D3
6,000 IU of vitamin D3 by mouth daily until the subject's serum 25(OH) level is ≥ 40ng/mL at which point the supplementation dose is reduced to 4,000 IU/day. Note: Subjects weighing <40 kilograms (kg) at study entry will receive their dose five days a week and all other subjects seven days a week.
Drug: High-Dose Vitamin D3
Subjects will receive 6,000 IU of vitamin D3 by mouth daily 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. Note: Subjects weighing <40 kilograms (kg) at study entry will receive their dose five days a week and all other subjects seven days a week.
Other Names:
  • High-Dose Cholecalciferol (D3)
  • high-dose vitamin D
Active Comparator: Standard-Dose Vitamin D3
400 IU/day of vitamin D3 by mouth daily
Drug: Standard-Dose Vitamin D3
Subjects will receive 400 IU/day of vitamin D3 daily by mouth.
Other Names:
  • Standard-Dose Cholecalciferol (D3)
  • standard-dose vitamin D

Detailed Description:

This is a multi-center, phase II, 18-week, two arm, unblinded randomized clinical trial.

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 for symptoms of 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 their clinical research 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-hydroxyvitamin D [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 (MMF), azathioprine, methotrexate, antimalarial medications (e.g., hydroxychloroquine), cyclosporine A (CsA), tacrolimus, intravenous immune globulin (IVIG), and abatacept.
  • Body weight > 25 kg
  • Able to swallow pills
  • 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 daily 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 upper limit of normal (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
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709474

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Lucile Packard Children's Hospital, Stanford University
Palo Alto, California, United States, 94304
UCSF School of Medicine
San Francisco, California, United States, 94143
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Columbia University
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75235
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98101
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

Additional 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: October 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
SLE
Vitamin D3
Vitamin D deficiency
IFN alpha expression

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

ClinicalTrials.gov processed this record on October 23, 2014