Efficacy of Vitamin D Supplementation in Bariatric Surgery Patients

• ClinicalTrials.gov Identifier: NCT01385098
• Recruitment Status: Completed
• First Posted: June 29, 2011
• Results First Posted: January 23, 2018
• Last Update Posted: January 23, 2018
• Sponsor: Vadim Sherman, MD
• Collaborators: Texas Woman's University; The Methodist Hospital Research Institute
• Information provided by (Responsible Party): Vadim Sherman, MD, The Methodist Hospital Research Institute

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Obesity; Vitamin D Deficiency	Dietary Supplement: Vitamin D3 and Calcium	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Preoperative Vitamin D Status and Efficacy of Therapeutic Vitamin D Supplementation Postoperatively in Bariatric Surgery Patients
• Study Start Date: July 2011
• Actual Primary Completion Date: May 2013
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vitamin D3 and Calcium; Dietary supplement of vitamin D3 and calcium	Dietary Supplement: Vitamin D3 and Calcium; 1500 mg of calcium citrate plus 1000 IU of vitamin D3 and 1000 IU of vitamin D3 bariatric supplements per day; Other Names: Celebrate ® calcium citrate plus vitamin D3; Celbrate ® multi-vitamin

Outcome Measures

Primary Outcome Measures :

1. Vitamin D Concentrations, Pre Operative and Post Bariatric Surgery Following 12 Weeks of Vitamin D Supplementation [ Time Frame: baseline and 12 weeks ]
   Serum 25(OH)D ng/ml levels at baseline and 12 weeks following bariatric surgery

Secondary Outcome Measures :

1. Serum 25-hydroxyvitamin D Levels at Baseline and 12 Weeks of Daily Vit D Supplementation Post Roux-en Y OR Sleeve Gastrectomy [ Time Frame: Baseline and 12 weeks ]
   We anticipate that vitamin D supplementation of Roux-en Y bariatric surgery patients will be less effective in improving or maintaining vitamin D status.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria: Adult female obese patients undergoing either Roux-en Y gastric bypass or sleeve gastrectomy at The Methodist Hospital may participate in the study. Obese patients with a body mass index (BMI) > 40 or BMI >35 with a co-morbidity will be eligible.

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Exclusion Criteria:Subjects will be excluded if they have evidence of vitamin D deficiency (< 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.

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Contacts and Locations

Locations

United States, Texas

The Methodist Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

Vadim Sherman, MD

Texas Woman's University

The Methodist Hospital Research Institute

Investigators

• Study Chair: Susan Miller, MD; The Methodist Hospital Research Institute
• Principal Investigator: Vadim Sherman, MD; The Methodist Hospital Research Institute

More Information

Publications of Results:

Moore CE, Sherman V. Vitamin D supplementation efficacy: sleeve gastrectomy versus gastric bypass surgery. Obes Surg. 2014 Dec;24(12):2055-60. doi: 10.1007/s11695-014-1261-7.

Other Publications:

Carlin AM, Rao DS, Yager KM, Parikh NJ, Kapke A. Treatment of vitamin D depletion after Roux-en-Y gastric bypass: a randomized prospective clinical trial. Surg Obes Relat Dis. 2009 Jul-Aug;5(4):444-9. doi: 10.1016/j.soard.2008.08.004. Epub 2008 Aug 14.

Compher CW, Badellino KO, Boullata JI. Vitamin D and the bariatric surgical patient: a review. Obes Surg. 2008 Feb;18(2):220-4. doi: 10.1007/s11695-007-9289-6. Epub 2008 Jan 5. Review.

Gemmel K, Santry HP, Prachand VN, Alverdy JC. Vitamin D deficiency in preoperative bariatric surgery patients. Surg Obes Relat Dis. 2009 Jan-Feb;5(1):54-9. doi: 10.1016/j.soard.2008.07.008. Epub 2008 Jul 24.

Mechanick JI, Kushner RF, Sugerman HJ, Gonzalez-Campoy JM, Collazo-Clavell ML, Guven S, Spitz AF, Apovian CM, Livingston EH, Brolin R, Sarwer DB, Anderson WA, Dixon J. American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient. Surg Obes Relat Dis. 2008 Sep-Oct;4(5 Suppl):S109-84. doi: 10.1016/j.soard.2008.08.009. Epub 2008 Aug 19. Erratum in: Surg Obes Relat Dis. 2010 Jan-Feb;6(1):112.

Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement. Am J Clin Nutr. 1992 Feb;55(2 Suppl):615S-619S. doi: 10.1093/ajcn/55.2.615s.

• Responsible Party: Vadim Sherman, MD, Sponsor-Investigator/Principal Investigator, The Methodist Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT01385098
• Other Study ID Numbers: Pro00005625; 0311-0034 ( Other Identifier: HMRI IRB )
• First Posted: June 29, 2011
• Results First Posted: January 23, 2018
• Last Update Posted: January 23, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vadim Sherman, MD, The Methodist Hospital Research Institute:

Vitamin D; Bariatric surgery; Roux-en Y surgery; Gastric sleeve surgery; Parathyroid Hormone

Additional relevant MeSH terms:

Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Calcium, Dietary; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Calcium; Micronutrients; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Bone Density Conservation Agents