Clinical trial NCT01331148: High Dose Vitamin D for Sickle Cell Disease
Official title: Pilot Study of Vitamin D to Ameliorate Chronic Pain in Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: sickle cell disease
vitamin D
pediatrics
pain
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Children's Healthcare of Atlanta
name: Emory University
First posted: 2011-04-07
Enrollment: 46
Sex: ALL
Minimum age (years): 7
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized placebo controlled double blind
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria:

* all sickle cell genotypes including SS, SB0thal, SC, SB+Thal
* Age 7-21 years old
* Last PRBC transfusion \>30 days prior

Exclusion Criteria:

* chronic renal failure
* chronic liver disease
* recent hospitalization \<14 days
* history of malignancy
* serum calcium level as defined in protocol section D 2.2
* treatment with concommitant medications as defined in section D 2.2 of the protocol
* known malabsorption or short gut syndrome or conditions associated with poor GI absorption
* patients currently on high dose vitamin D therapy

Primary outcomes:
measure: 25 (OH)D in Nmol/L Between Baseline and 6 Months
timeFrame: Baseline and after 6 months of study participation
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
Study officials:
affiliation: Wake Forest University Health Sciences
name: Ifeyinwa Osunkwo, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Osunkwo I, Ziegler TR, Alvarez J, McCracken C, Cherry K, Osunkwo CE, Ofori-Acquah SF, Ghosh S, Ogunbobode A, Rhodes J, Eckman JR, Dampier C, Tangpricha V. High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study. Br J Haematol. 2012 Oct;159(2):211-5. doi: 10.1111/bjh.12019. Epub 2012 Aug 28.