Clinical trial NCT04279392: Healthy Body, Healthy Bones After Bariatric Surgery Trial
Official title: Feasibility of Bisphosphonate Use on Sleeve Gastrectomy Associated Bone Loss: Healthy Body, Healthy Bones Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Bariatric Surgery Candidate
Bone Loss
Bone Resorption
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2020-02-21
Enrollment: 10
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In this randomized controlled trial each subject will be randomized (1:1, block randomization with a block size of 10) to one treatment group (Active or Inactive treatment) and will be considered part of the intent-to-treat (ITT) cohort. The research pharmacist will be responsible for completing the randomization process, and will hold the group assignment data. All other study personnel will be blinded to group assignment.
Primary purpose: PREVENTION

Brief summary: One in three adults in the United States suffers from obesity. Bariatric surgery is an increasingly utilized and effective treatment for obesity and obesity-related comorbidities, however, the massive weight loss associated with bariatric surgery adversely affects bone leads to an increased risk of fracture. Bisphosphonate medications, such as zoledronic acid, are used to treat bone loss in patients with osteoporosis, and this study investigates whether this medication can prevent bone loss associated with surgical weight loss procedures.

Detailed description: One in three adults in the United States suffers from obesity. Bariatric surgery is an increasingly utilized and effective treatment for obesity and obesity-related comorbidities, however, the massive weight loss associated with bariatric surgery adversely affects bone metabolism. Significant decreases in bone mineral density lead to an increased risk of fracture and subsequent reduction in physical function among bariatric surgery patients. Bisphosphonate medications, such as zoledronic acid, have been evaluated for safety and efficacy in combating bone loss in patients with osteoporosis, but their use in bariatric surgery-induced bone loss has not been explored. The primary goal of this study is to investigate whether bisphosphonate therapies are able to combat bone loss associated with surgical weight loss procedures. This research proposal is a 1-year, pilot randomized controlled trial (RCT) involving 30 adult sleeve gastrectomy patients randomized to receive either a one-time zoledronic acid infusion or placebo (n=15 per group). The investigators hypothesize that zoledronic acid, a standard treatment for low bone density, will be an effective intervention to reduce sleeve gastrectomy-induced bone loss. Bone loss is an unintended consequence of an otherwise life-saving procedure, with declining bone health potentially contributing to major morbidity in those undergoing a bariatric procedure. Identifying effective interventions to minimize bone loss is crucial for comprehensive treatment of patients who undergo bariatric surgery. Specific Aim 1: To determine the efficacy of zoledronic acid in preventing bone loss associated with sleeve gastrectomy (SG). Bone mineral density (BMD) and bone turnover markers will be measured at baseline and 9 months. The primary outcome is change in BMD as measured by Dual-energy x-ray absorptiometry (DXA). Secondary outcomes are change in BMD as measured by Quantitative Computed Tomography (QCT) and change in the serum bone turnover markers, urinary collagen type 1 cross-linked N-telopeptide (CTX; bone formation marker), serum type 1 procollagen N-terminal (P1NP; bone resorption marker), sclerostin, and osteocalcin. Specific Aim 2: To evaluate the feasibility of this trial in those who have undergone SG surgery. The feasibility will be assessed by documenting adverse events and compliance rates of the intervention at each study time point.

Eligibility criteria: Inclusion Criteria:

* Subjects planning a sleeve gastrectomy procedure at the University of Nebraska Medical Center (UNMC) Bariatric Center
* Agreement to all study procedures and assessments
* Women must be postmenopausal (FSH blood level \> 30 mIU/m), or incapable of child-bearing

Exclusion Criteria:

* Prior bariatric surgery
* \< 19 years of age
* Weight ≥ 350lbs
* Liver or renal disease
* Hypercalcemia, hypocalcemia, or hypomagnesemia
* Serum 25-OH vitamin D \< 20 ng/mL
* History of bone-modifying disorders
* Use of bone-active medications
* Known sensitivity to bisphosphonates
* Extensive dental work involving extraction or dental implant within the past 2 months or planned in the upcoming 6 months
* Current diagnosis of type 1 diabetes
* Current malignancy
* Autoimmune disease impacting bone (ex: Rheumatoid Arthritis)

Primary outcomes:
measure: Change in Hip Bone Mineral Density (BMD)
timeFrame: baseline and 10 months post-surgery
Secondary outcomes:
measure: Change in Lumbar Spine Bone Mineral Density (BMD)
timeFrame: baseline and 10 months post-surgery
measure: Change in Trunk Lean Mass
timeFrame: baseline and 9 months post-surgery
measure: Change in Trunk Fat Mass
timeFrame: baseline and 9 months post-surgery
measure: Change in Weight
timeFrame: baseline and 9 months post-surgery
Other outcomes:
measure: Proportion of Participants Completing 9 Month Study Visit Requirements
timeFrame: 9 Months
measure: Tolerance: Total Number of Adverse Events Reported by Participants in the Active and In-active Arms
timeFrame: 9 Months
Locations:
city: Omaha
country: United States
facility: Bariatric Center, Nebraska Medicine
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Laura D Bilek, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Flores LE, Mack L, Wichman C, Weaver AA, Kothari V, Bilek LD. Protocol for a pilot randomised controlled trial of zoledronic acid to prevent bone loss following sleeve gastrectomy surgery. BMJ Open. 2021 Dec 9;11(12):e057483. doi: 10.1136/bmjopen-2021-057483.