Vitamin D3 Treatment in Pediatric Systemic Lupus Erythematosus
Status: | Terminated |
---|---|
Conditions: | Lupus |
Therapuetic Areas: | Immunology / Infectious Diseases |
Healthy: | No |
Age Range: | 5 - 20 |
Updated: | 4/21/2016 |
Start Date: | June 2013 |
End Date: | July 2014 |
Vitamin D3 Effects on Immune Function in Pediatric Systemic Lupus Erythematosus (SLE)
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.
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.
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 high-dose (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.
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 high-dose (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.
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 rituximab or
belimumab criterion, below);
- Significant renal insufficiency defined as:
- Estimated GFR < 60 mL/min/1.73m^2 or estimated GFR < 90 mL/min/1.73m^2 with a
reduction of the GFR by > 15% from the last measurement;
- 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 (influenza) vaccination within one week prior to randomization.
We found this trial at
13
sites
Columbia University In 1897, the university moved from Forty-ninth Street and Madison Avenue, where it...
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Montefiore Medical Center As the academic medical center and University Hospital for Albert Einstein College...
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University of Chicago One of the world's premier academic and research institutions, the University of...
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Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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University of Rochester The University of Rochester is one of the country's top-tier research universities....
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225 E Chicago Ave
Chicago, Illinois 60611
Chicago, Illinois 60611
(312) 227-4000

Ann & Robert H. Lurie Children's Hospital of Chicago Ann & Robert H. Lurie Children
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Children's Medical Center of Dallas Children's Medical Center is private, not-for-profit, and is the fifth-largest...
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Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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Riley Hospital for Children Riley Hospital for Children at IU Health is a place of...
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725 Welch Rd
Palo Alto, California 94304
Palo Alto, California 94304
(650) 497-8000
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Lucile Packard Children's Hospital Stanford University Stanford Children's Health is the only network in the...
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Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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