Efficacy of Vitamin D Supplementation in Bariatric Surgery Patients
Condition: Obesity; Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency
Study type: Interventional

Summary: 
      As the use of bariatric surgery for treatment of extreme obesity adults continues to rise,
      clinicians must be aware of pre-existing nutritional deficiencies in overweight and obese
      patients. Nutritional deficiencies are common in patients undergoing bariatric surgery and
      these deficiencies should be detected and addressed early to avoid post-operative
      complications. To improve long-term outcomes following bariatric surgery, nutritional
      screening and prescribing appropriate supplementation to prevent nutrient deficiencies is
      needed. Vitamin D deficiency is common following bariatric surgery and has been reported to
      occur in 50-80% bariatric patients.The goal of this pilot study is to help develop nutrient
      supplementation interventions following two types of bariatric surgery: Roux-en Y gastric
      bypass and sleeve gastrectomy.

      Recently, several studies in adults have revealed an inverse relationship between body fat
      and blood 25-hydroxyvitamin D3 [25(OH)D] levels, the relevant marker of low vitamin D status.
      Although vitamin D is well known for its essential role in bone metabolism and calcium
      homeostasis, increasing evidence is linking vitamin D to obesity. This study will evaluate
      vitamin D status during post operative daily supplementation of 2,000 IU of vitamin D3 and
      1500 mg of calcium through assessment of changes in serum 25(OH)D, parathyroid hormone (PTH),
      calcium and phosphorus at baseline, 4 weeks, and 12 weeks following surgery. The dietary
      contribution of vitamin D and calcium will be estimated by food records analyzed using the
      University of Minnesota 2010 Nutrition Data System for Research (NDSR) program.

      Primary Hypothesis: Daily supplementation with 2,000 IU of vitamin D3 for 12 weeks will
      significantly increase mean serum 25(OH)D levels in obese subjects following bariatric
      surgery compared to baseline levels.

      Secondary Hypothesis: The percent response above baseline to daily supplementation with 2,000
      IU of vitamin D3 will significantly differ between Roux-en Y and sleeve gastrectomy patients.
    

Detailed description: 
      The prospective pilot study is designed to evaluate vitamin D status pre-operatively and
      post-operatively in 37 female patients undergoing either Roux-en Y gastric bypass or sleeve
      gastrectomy at The Methodist Hospital with 32 patients expecting to complete the 12 week
      trial. Women scheduled for either of these two types of bariatric surgery will be considered
      for inclusion in the pilot study. Based on previous research experience at The Methodist
      Hospital, the majority of bariatric patients are women. No children are treated at the
      Methodist Hospital bariatric center.

      Subjects will be excluded if they have evidence of vitamin D deficiency (25(OH)D <20 ng/mL),
      hypercalcemia (calcium > 2.63 mmol/L), hypocalcemia (calcium < 1.75 mmol/L), renal
      insufficiency (GFR < 50 ml/min), or a history of primary hyperparathyroidism or renal tubular
      acidosis. Participants will be excluded if they take medications that interfere with vitamin
      D metabolism, have significant sun exposure, plan to travel to sunny climates during the
      study, or a history of hypercalcemia.

      Baseline measures of serum 25(OH)D, PTH, calcium and phosphorus will be obtained. Values will
      be determined one week prior to surgery and during the follow-up visit at 12 weeks
      postoperatively. In addition, 25(OH)D will be measured at the 4th week post-operative clinic
      visit. Baseline information obtained will include age, height (centimeter), weight
      (kilogram), body mass index, sex, and race or ethnicity. A full medication list and medical
      history to identify any co-morbid conditions will be collected. Participants will be
      instructed to avoid traveling to sunny locations during the 12 week study.

      Laboratory measurements pre-operative: 25(OH)D, PTH, CBC/Diff, glucose, calcium, albumin,
      total protein, sodium, potassium, CO2, BUN, creatinine, ALP, ALT, AST, bilirubin, lipid
      panel, ferritin, folate, iron, total iron binding capacity, hemoglobin A1c, insulin, vitamin
      B12, PT/PTT, TSH, HCG, C-reactive protein.

      Laboratory measurements at week 4: 25(OH)D

      Laboratory measurements at week 12: 25(OH)D, PTH, CBC/Diff, glucose, calcium, albumin, total
      protein, sodium, potassium, CO2, BUN, creatinine, ALP, ALT, AST, bilirubin, lipid panel,
      ferritin, folate, total iron binding capacity, vitamin B12, and TSH.

      Nutrient intake assessments: Dietary intake of macronutrients, vitamin D, calcium, and other
      micronutrients will be assessed using the University of Minnesota 2010 Nutrition Data System
      for Research (NDSR) program. NDSR is a comprehensive nutrient calculation software program
      used for research purposes. The NDSR database contains values for 160 nutrients and includes
      more than 18,000 foods.

      Participants' baseline laboratory will be used to measure the response to vitamin D and
      calcium supplementation over the course of 12 weeks. Bariatric patients participating in the
      study will be instructed to take a total of 1500 mg of calcium (as calcium citrate) plus 1000
      IU of vitamin D3 as three chewable tablets (Celebrate ®). An addition 1000 IU of vitamin D3
      per day will be taken as two chewable multi-vitamin bariatric supplements (Celebrate ®).
      Supplement compliance will be assessed by daily written records and inspection of supplement
      bottle containers at each clinic visit.

      Serum 25(OH)D will be measured by ARUP Laboratories (Salt Lake City, UT, USA) using a
      chemiluminescent immunoassay. Serum calcium and phosphorus will be determined by The
      Methodist Hospital Clinical Chemistry Department as part of the standard bariatric protocol
      comprehensive metabolic panel. Intact PTH (iPTH) assays will be performed using the ADVIA
      Centaur ® XP Immunoassay System.

      Vitamin D deficiency will be defined as 25(OH)D levels less than 20 ng/mL (50 nmol/L) and
      vitamin D insufficiency as 21 to 29 ng/mL (50 to 80 nmol/L). Secondary hyperparathyroidism
      will be defined as iPTH ≥ 70 ng/L. An increase in serum intact PTH level will be taken to be
      indicative of a possible negative calcium balance or a vitamin D deficiency (or both).
      Hypercalcemia will be defined as calcium > 2.63 mmol/L.

      Statistical analysis:

      Primary Hypothesis: Daily supplementation with 2,000 IU of vitamin D3 for 12 weeks will
      significantly increase mean serum 25(OH)D levels in obese subjects following bariatric
      surgery compared to baseline levels.

      Secondary Hypothesis: The percent response above baseline to daily supplementation with 2,000
      IU of vitamin D3 will significantly differ between Roux-en Y and sleeve gastrectomy patients.

      Subject Withdrawal:

      Participants will be withdrawn from the study if serum 25(OH)D levels are identified as
      within the deficient range so that the patient can receive needed treatment. A vitamin D
      deficiency will be defined as 25(OH)D concentrations less than 20 ng/mL (50 nmol/L) and
      vitamin D insufficiency as 21 to 29 ng/mL. In addition, if an abnormally high level of
      25(OH)D is obtained (200 ng/mL or 500 nmol/L), we will have the 25(OH)D measurement repeated.
      If the second test is confirmed to be high, then we will withdraw that particular patient
      from the study for medical follow-up. If we find a trend of excess vitamin D among
      participants, however, we will re-evaluate and consider termination of the study.
    

Intervention name(s): Vitamin D3 and Calcium
Intervention type(s): Dietary Supplement
Intervention description(s): 1500 mg of calcium citrate plus 1000 IU of vitamin D3 and 1000 IU of vitamin D3 bariatric supplements per day
Other intervention name(s): Celebrate ® calcium citrate plus vitamin D3; Celbrate ® multi-vitamin
Intervention MeSH terms: Calcium, Dietary; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Calcium
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Vitamin D; Bariatric surgery; Roux-en Y surgery; Gastric sleeve surgery; Parathyroid Hormone