High Dose Vitamin D for Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      Vitamin D deficiency (VDD) is very common among African American adolescents and adults in
      the US, ten times higher than is seen in Caucasians. VDD is also quite common in sickle cell
      disease (SCD). Both VDD and SCD can cause chronic pain, compression fractures, and muscle
      weakness. The investigators believe VDD may contribute to poor musculoskeletal health and
      chronic pain seen in pediatric SCD. In this study, the investigators aim to show that
      children and adolescents with SCD and chronic pain have lower levels of vitamin D compared to
      those without chronic pain. The investigators also aim to determine the clinical
      characteristics in SCD patients related to their vitamin D status.

      About 60 subjects (7 to 21 years old) will be enrolled on this study, 30 with chronic pain
      and 30 without chronic pain. The investigators will assess baseline characteristics including
      vitamin D levels, bone turnover rates (measured by C telopeptide blood levels [CTx]), markers
      of inflammation and oxidative stress levels in blood, baseline hemoglobin and other
      laboratory parameters, presence of abnormal bones on chest x-ray, pulmonary function, opioid
      analgesic use, overall muscle strength, quality of life and depression.

      To evaluate the impact of vitamin D replacement on these baseline characteristics, the
      investigators will randomize subjects to receive either placebo or high dose vitamin D for 6
      weeks after which time the investigators will evaluate overall vitamin D status, muscle and
      bone health, depression, quality of life, pain status and use of opioid pain medications,
      inflammation and oxidative status comparing before and after treatment with high dose vitamin
      D. The investigators will give-at no cost to subjects-a daily supplement that will provide
      the recommended daily allowance of calcium and vitamin D that contains 500mg Calcium and
      200IU vitamin D to subjects throughout the study period. Subjects will be in the study for 7
      months and have five to six study visits.
    

Detailed description: 
      Nearly 43% of African American adults and 53-70% of African American adolescents in the US
      have vitamin D deficiency (VDD), ten times more than is seen in Caucasians. VDD is also quite
      common in sickle cell disease (SCD) with prevalence rates of 65-100%. Pain is a hallmark
      symptoms of SCD accounting for the majority of SCD morbidity. Some patients with SCD develop
      debilitating chronic pain with an unclear etiology and unsatisfactory response to treatment.
      Both VDD and SCD can cause chronic pain, compression fractures and myopathy. We hypothesize
      that VDD is implicated in the poor musculoskeletal health and chronic pain of SCD. Therefore
      we aim [1] to demonstrate that pediatric sickle cell patients have high rates of VDD and
      those with chronic pain have lower levels of vitamin D compared to those without chronic pain
      [2] to evaluate the musculoskeletal health, pain status, opioid analgesic use, depression and
      quality of life in SCD patients with and without chronic pain and determine if the presence
      or severity of VDD is associated with a more severe clinical phenotype and [3] to demonstrate
      that administration of replacement doses of vitamin D will correct VDD, improve
      musculoskeletal health and ameliorate chronic pain. An additional aim of this project is to
      [4] evaluate and describe any correlates between vitamin D status and serum levels of
      inflammatory cytokines, markers of oxidative stress and vitamin D receptor polymorphisms in
      SCD patients with and without chronic pain.

      We will evaluate 60 SCD subjects aged 7-21 years (30 with chronic pain and 30 without chronic
      pain) for VDD and to determine specific baseline characteristics including 25(OH)D levels,
      bone turnover rates measured by C telopeptide serum levels (CTx), opioid analgesic use,
      neuromuscular strength, evidence of skeletal complications on chest radiograph, depression
      and quality of life, serum levels of inflammatory cytokines and oxidative status and
      characteristics of the vitamin D receptor (VDR). These characteristics will be compared
      between those with chronic pain and those without chronic pain. We will have a 30 day run in
      observation period during which baseline pain status will be determined by daily pain diary
      report. All subjects with then be randomly assigned to receive vitamin D replacement therapy
      or placebo for six weeks and prospectively followed for six months. All subjects will be
      given daily recommended daily allowance (RDA) of calcium and vitamin D in the form of a soft
      chew containing 500 mg calcium and 200 IU vitamin D throughout the study period. The primary
      endpoints are changes in serum 25(OH)D and CTx levels and opioid analgesic use (mg/kg
      morphine equivalent). Secondary endpoints include changes in pain status as documented by
      diary, depression scores, quality of life scores, neuromuscular strength and changes in serum
      cytokine levels and markers of oxidative stress.

      In this study we hypothesize that VDD either contributes to or exacerbates sickle cell
      chronic pain and that correcting VDD in SCD will result in decreased pain, depression and
      opioid analgesic use; an improvement in musculoskeletal health; as well as a reduction in
      degree of inflammation and oxidative stress. This is a pilot study in preparation for a
      larger prospective trial evaluating the role of VDD in the pathobiology of SCD pain and
      musculoskeletal health.
    

Intervention name(s): Vitamin D; Placebo
Intervention type(s): Drug; Other
Intervention description(s): 10,000 IU/caplet, patients receiving 240,000 IU to 600,000 IU cumulative Vitamin D dose based on weight.; placebo with daily calcium/Vitamin D soft chews
Other intervention name(s): cholecalciferol
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: randomized placebo controlled double blind
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: sickle cell disease; vitamin D; pediatrics; pain