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Effect of Vitamin D Status and Repletion on Postoperative Total Joint Arthroplasty Complications

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ClinicalTrials.gov Identifier: NCT04229368
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : January 27, 2021
Sponsor:
Collaborators:
Massachusetts General Hospital
Newton-Wellesley Hospital
Information provided by (Responsible Party):
Antonia Faustina Chen, Brigham and Women's Hospital

Brief Summary:
Vitamin D status has been shown to have an effect on post-operative outcomes in total joint arthroplasty. The goal of this study is to determine if pre-operative supplementation and correction of Vitamin D deficiency can reduce postoperative complications.

Condition or disease Intervention/treatment Phase
Hip Arthropathy Knee Arthropathy Vitamin D Deficiency Dietary Supplement: Vitamin D3 Not Applicable

Detailed Description:

Total joint arthroplasty (TJA) is one of the most common surgical procedures performed in the United States (US), with approximately 2.5 million individuals with total hip arthroplasties (THAs) and 4.7 million individuals with total knee arthroplasties (TKAs) in 2010. Patients who undergo TJA commonly have Vitamin D deficiency, with rates reported to be 24-61% in primary TJA patients. Vitamin D deficiency affects women and minorities at high rates, in addition to non-Hispanic whites. Previous studies demonstrated that Vitamin D deficiency poorly impacts outcomes after various surgical procedures. Specifically in TJA patients, recent studies show a higher rate of Vitamin D deficiency in periprosthetic joint infection (PJI) patients, and a higher rate of postoperative complications and infection in revision TJA patients with low Vitamin D. In a PJI mouse model, Vitamin D-deficient mice were shown to have an increased bacterial burden when compared to Vitamin D-deficient mice that received "rescue" cholecalciferol (Vitamin D3) supplementation. Bacterial burden was similarly decreased between normal mice and the Vitamin D-deficient "rescue" mice receiving supplementation. A single dose of Vitamin D3 supplementation in Vitamin D-deficient mice using the same mouse model reversed the effect of PJI by decreasing bacterial burden and neutrophil infiltration.

The serum concentration of 25-hydroxycholecalciferol or 25-hydroxyvitamin D (25(OH)D) is the most accurate measure of stores of Vitamin D in the body. There are currently different recommendations regarding the optimal serum 25(OH)D level for bone health, the optimal daily intake of Vitamin D, and the treatments for Vitamin D deficiency or insufficiency. These controversial topics do not provide clear clinical guidance on how to optimize Vitamin D levels in surgical patients to reduce complication rates. The US Institute of Medicine (IOM) committee recommended a 25(OH)D level >20 ng/mL but other organizations recommend ≥30 ng/mL. At present, deficient levels of Vitamin D are generally defined as a 25(OH)D <20 ng/ml, relative insufficiency as 20 to 29 ng/mL, and sufficient levels as ≥ 30 ng/ml. In 2011, the IOM established Recommended Dietary Allowances (RDAs) for Vitamin D of 600-800 IU/d in order to achieve a 25(OH)D level of 20 ng/ml for 97.5% of the general population. The debate concerns recommendations based upon population science, in contrast to care of an individual patient. Thus, there is continuing debate among several groups that recommend higher Vitamin D3 doses and 25(OH)D levels of ≥30 ng/mL for optimal bone health and in high-risk individuals with osteoporosis. The National Osteoporosis Foundation recommends 800 to 1000 IU Vitamin D3 daily for adults aged 50 years and older, as do the International Osteoporosis Foundation and Endocrine Society. The Endocrine Society recommended even higher doses up to 1500 to 2000 IU/d of Vitamin D3 for older adults. For Vitamin D deficiency, the recommended treatment is 50,000 units of Vitamin D3 weekly for 8 weeks with an assay repeat to determine whether Vitamin D-sufficiency ≥30ng/mL was achieved. The proposed study was designed in light of debated recommendations in the literature and should result in rigorous new information about 25(OH)D levels achieved with different doses of Vitamin D3 supplementation and their impact on post-TJA complications.

There are no current studies in literature examining whether preoperative supplementation and correction of Vitamin D deficiency may reduce complications following TJA. The aim of this randomized controlled trial is to evaluate the ability of different doses (low and high dose) of Vitamin D3 supplementation to affect adverse events and functional outcomes following total joint arthroplasty surgery. To conduct this study, investigators propose randomizing subjects with 25(OH)D levels between 10 and 29 ng/mL to receive different doses of Vitamin D to assess the effects of Vitamin D3 supplementation dosage on postoperative TJA complication rates. Consented patients with serum 25(OH)D levels equal or greater than 30 ng/dL will be included in the control group.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 900 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 900 patients to be enrolled total including controls, and two additional study arms
Primary Purpose: Prevention
Official Title: Effect of Vitamin D Status and Repletion on Postoperative Total Joint Arthroplasty Complications
Actual Study Start Date : September 1, 2019
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : July 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Low Vitamin D3 Supplementation
Subjects enrolled into Group 1 (low-dose Vitamin D3 supplementation) will receive 800 IU of oral Vitamin D3 (Cholecalciferol) daily for 4 weeks prior to surgery, followed by 800 IU of oral Vitamin D3 daily for 3 months after surgery. Vitamin D3 supplementation will be given for a total of 4 months. Supplementing Vitamin D-deficient patients with a minimum of 800 IU of Vitamin D3 daily is supported by the IOM.
Dietary Supplement: Vitamin D3
Vitamin D will be given at doses commonly given to patients with low vitamin D levels
Other Name: cholecalciferol

Active Comparator: High Vitamin D3 Supplementation
Subjects enrolled into Group 2 (high-dose Vitamin D3 supplementation) will receive 50,000 IU of oral Vitamin D3 (Cholecalciferol) twice per week for 1 weeks followed by 50,000 IU once per week for 3 weeks prior to surgery. After surgery they will receive 50,000 IU of oral Vitamin D3 once per week for 4 weeks followed by 800 IU daily for 8 weeks. Vitamin D3 supplementation will be given for a total of 4 months.
Dietary Supplement: Vitamin D3
Vitamin D will be given at doses commonly given to patients with low vitamin D levels
Other Name: cholecalciferol

No Intervention: No supplementation
Subjects with serum 25(OH)D level ≥30ng/mL will not receive any Vitamin D supplementation both pre- and postoperatively, as these are considered sufficient. These control patients will be asked to take any supplements containing Vitamin D for the duration of their participation in the trial. All patients in group 3 will have their serum 25(OH)D checked at 3 months after the surgery.



Primary Outcome Measures :
  1. Readmission, reoperation, wound complications, and PJI [ Time Frame: Preoperative visit to three months post-op ]
    adverse events


Secondary Outcome Measures :
  1. Vitamin D status [ Time Frame: Day of surgery to to three months post-op ]
    Vitamin D levels will be drawn initially, during supplementation and following

  2. Patient-Reported Outcomes Measurement Information System (PROMIS) [ Time Frame: Preoperative visit to three months post-op ]
    set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children.41 to 78.3 with higher scores representing worse pain impact.

  3. Pain Levels: visual analog scale (VAS) [ Time Frame: Preoperative visit to three months post-op ]
    Scores on the VAS pain scale range from 0-10 with 0 being no pain and 10 being the highest pain level imaginable.

  4. Hip disability and Osteoarthritis Outcome Score (HOOS) [ Time Frame: Preoperative visit to three months post-op ]
    Scores range from 0 to 100 with a score of 0 indicating the worst possible hip symptoms and 100 indicating no hip symptoms



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients ≥18 years of age undergoing elective unilateral primary TJA for osteoarthritis
  • Patients with a pre-operative serum 25(OH)D levels ≥10 ng/mL
  • Patients who consent to the study

Exclusion Criteria:

  • Adult patients ≥18 years of age undergoing elective primary TJA with a pre-operative serum 25(OH)D2,3 level <10 ng/mL
  • Patients undergoing revision surgery
  • Patients lacking mental capacity to comply with study procedures
  • Patients with serum 25(OH)D levels between 10-29 ng/dL refusing to stop their current Vitamin D and multivitamins supplementations
  • Hypercalcemia (total calcium >10.6 mg/dL or ionized serum calcium >5.4mg/dL)
  • History of nephrolithiasis
  • Granulomatous disease
  • Dialysis and advanced kidney disease
  • Previous infection/septic arthritis
  • Inability to swallow Vitamin D3 pills
  • Allergy to Vitamin D3 (It is estimated that 1 in 300 individuals may have an allergy with skin manifestations 17)
  • Hypocalcemia (<8.5 mg/dL)
  • Chronic kidney disease (eGFR <60 mL/minute)
  • Known hyperparathyroidism
  • Known osteoporosis/insufficiency stress fractures (if normal stresses are applied to an abnormal bone)
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04229368


Contacts
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Contact: Antonia F Chen, MD 617-525-5935 afchen@bwh.harvard.edu

Locations
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United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Antonia F Chen, MD, MBA    617-525-5935    afchen@bwh.harvard.edu   
Principal Investigator: Antonia F Chen, MD, MBA         
Sponsors and Collaborators
Brigham and Women's Hospital
Massachusetts General Hospital
Newton-Wellesley Hospital
Investigators
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Principal Investigator: Antonia F Chen, MD Brigham and Women's Hospital
Publications:

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Responsible Party: Antonia Faustina Chen, Director of Research Arthroplasty Division, Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT04229368    
Other Study ID Numbers: 2018P001701
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: January 27, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Antonia Faustina Chen, Brigham and Women's Hospital:
joint replacement
hip arthroplasty
knee arthroplasty
clinical outcomes
Vitamin D Deficiency
Additional relevant MeSH terms:
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Joint Diseases
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Musculoskeletal Diseases
Vitamin D
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents