Risedronate for Bone Loss After Bariatric Surgery
(WE RISE U01 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Wake Forest University Health Sciences
Must not be taking: Growth hormones, Oral steroids
Disqualifiers: Weight > 450 lbs, Allergies, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?The purpose of this research study is to see whether receiving a bisphosphonate medication called risedronate can reduce bone and muscle loss following bariatric surgery. Participation will involve up to 6 study visits and last about 1 year. Risedronate is a medication that prevents bone breakdown and has been approved by the US Food and Drug Administration (FDA) for the prevention and treatment of osteoporosis in older men and women. However, risedronate has not been approved for the prevention of bone and muscle loss following vertical sleeve gastrectomy.
Participation in this study will involve completing two visits before beginning the intervention. Participants who qualify will be scheduled to begin the intervention program which will involve taking 6 monthly doses of a risedronate or placebo pill. Participants will then receive monthly contacts by study staff during this time to remind participants to take the intervention pill and ask about any adverse events. After the completion of intervention period, participants will complete up to 4 follow up study visits at 6 months (2 visits) and at 12 months (2 visits).
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you regularly use growth hormones, oral steroids, or prescription osteoporosis medications.
What data supports the effectiveness of the drug Risedronate for preventing bone loss after bariatric surgery?
The pilot study suggests that using Risedronate, a type of bisphosphonate, is feasible and well-tolerated for preventing bone loss after sleeve gastrectomy, a common type of bariatric surgery. Bisphosphonates are known to reduce fracture risk in osteoporosis, which supports their potential use in minimizing bone loss after bariatric surgery.
12345Is risedronate safe for humans?
Risedronate is generally well-tolerated and has a safety profile similar to a placebo in clinical studies, even in patients with a history of gastrointestinal issues. It has been used safely in treating osteoporosis and preventing bone loss in various conditions.
678910How is the drug Risedronate unique for treating bone loss after bariatric surgery?
Risedronate is a potent bisphosphonate that works by inhibiting osteoclasts (cells that break down bone), which helps preserve bone density and reduce fracture risk. It is unique because it acts quickly, showing significant effects within 6 months, and has a lower risk of causing stomach ulcers compared to similar drugs like alendronate.
678911Eligibility Criteria
This trial is for individuals who have undergone sleeve gastrectomy and are willing to follow the study procedures. They must be able to get themselves to study visits, weigh less than 450 lbs, and not require assistance with positioning on a scanner. Participants should not be in another research study or regularly use certain medications like growth hormones, steroids, or osteoporosis drugs.Inclusion Criteria
Willing to provide informed consent
Agree to all study procedures and assessments.
I have had a sleeve gastrectomy.
Exclusion Criteria
I need help to position myself on a medical scanner.
You weigh more than 450 pounds.
Current participation in other research study
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
2 visits (in-person)
Treatment
Participants receive six monthly doses of risedronate or placebo
6 months
Monthly contacts (virtual)
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
4 visits (in-person)
Participant Groups
The trial is testing if risedronate can prevent bone and muscle loss after bariatric surgery. Over one year, participants will take either risedronate or a placebo pill monthly while being monitored through six visits and regular check-ins by the study team.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: BisphosphonateExperimental Treatment1 Intervention
Participants in this arm will receive six months of 150 mg once monthly oral risedronate
Group II: PlaceboPlacebo Group1 Intervention
Participants in this arm will receive six months of placebo
Risedronate is already approved in United States for the following indications:
🇺🇸 Approved in United States as Actonel for:
- Postmenopausal osteoporosis
- Glucocorticoid-induced osteoporosis
- Male osteoporosis
- Paget disease
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Wake Forest School of MedicineWinston-Salem, NC
Loading ...
Who Is Running the Clinical Trial?
Wake Forest University Health SciencesLead Sponsor
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Collaborator
References
Risedronate to Prevent Bone Loss After Sleeve Gastrectomy: Study Design and Feasibility Report of a Pilot Randomized Controlled Trial. [2022]Mounting evidence implicates bariatric surgery as a cause of increased skeletal fragility and fracture risk. Bisphosphonate therapy reduces osteoporotic fracture risk and may be effective in minimizing bone loss associated with bariatric surgery. The main objective of this pilot randomized controlled trial (RCT; Clinical Trial No. NCT03411902) was to determine the feasibility of recruiting, treating, and following 24 older patients who had undergone sleeve gastrectomy in a 6 month RCT examining the efficacy of 150-mg once-monthly risedronate (versus placebo) in the prevention of surgical weight-loss-associated bone loss. Feasibility was defined as: (i) >30% recruitment yield, (ii) >80% retention, (iii) >80% pills taken, (iv) <20% adverse events (AEs), and (v) >80% participant satisfaction. Study recruitment occurred over 17 months. Seventy participants were referred, with 24 randomized (34% yield) to risedronate (n = 11) or placebo (n = 13). Average age was 56 ± 7 years, 83% were female (63% postmenopausal), and 21% were black. The risedronate group had a higher baseline BMI than the placebo group (48.1 ± 7.2 versus 41.9 ± 3.8 kg/m2). The 10-year fracture risk was low (6.0% major osteoporotic fracture, 0.4% hip fracture); however, three individuals (12.5%, all risedronate group) were osteopenic at baseline. Twenty-one participants returned for 6-month follow-up testing (88% retention) with all (n = 3) loss to follow-up occurring in the risedronate group. Average number of pills taken among completers was 5.9 ± 0.4 and 6.0 ± 0.0 in the risedronate and placebo groups, respectively (p = 0.21), with active participants taking >80% of allotted pills. Five AEs (3.7% AE rate) were reported; one definitely related, four not related, and none serious. All participants reported high satisfaction with participation in the study. Use of bisphosphonates as a novel therapeutic to preserve bone density in patients who had undergone a sleeve gastrectomy appears feasible and well-tolerated. Knowledge gained from this pilot RCT will be used to inform the design of an appropriately powered trial.
Zoledronic acid for prevention of bone loss in patients receiving bariatric surgery. [2022]Bariatric surgery is an effective treatment for severe obesity but causes substantial bone loss and increased risk of fractures. To date, there have been no studies examining whether pharmacologic treatments can prevent bone loss after bariatric surgery. We performed an exploratory study to examine the preliminary safety and efficacy of zoledronic acid (ZOL), a potent anti-resorptive bisphosphonate, to suppress bone turnover markers (BTM) and prevent declines in bone mineral density (BMD) after Roux-en-Y gastric bypass (RYGB) surgery.
Strategies to reduce the onset of sleeve gastrectomy associated bone loss (STRONG BONES): Trial design and methods. [2023]Despite recognized improvements in obesity-related comorbidities, mounting evidence implicates surgical weight loss in the onset of skeletal fragility. Sleeve gastrectomy (SG) is the most commonly performed bariatric procedure and is associated with 3-7% axial bone loss in the year following surgery. Bisphosphonates are FDA-approved medications for the prevention and treatment of age-related bone loss and may represent a strategy to reduce bone loss following SG surgery.
MANAGEMENT OF ENDOCRINE DISEASE: Bone complications of bariatric surgery: updates on sleeve gastrectomy, fractures, and interventions. [2023]Despite well recognized improvements in obesity-related comorbidities, increasing evidence implicates bariatric surgery in the onset of adverse skeletal health outcomes. The purpose of this review is to provide a focused update in three critical areas: (i) emergent data on sleeve gastrectomy and bone loss, (ii) evidence linking bariatric surgery to incident fracture, and (iii) intervention strategies designed to mitigate surgical bone loss. Better understanding of these issues will inform our treatment of skeletal health for patients planning bariatric surgery.
Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis. [2023]Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D
[Treatment of osteoporosis by risedronate-- speed, efficacy and safety]. [2018]Risedronate (Actonel 35 mg), which was promoted in Croatia a few months ago, is the latest (III) generation of bisphosphonates, the most efficient anti-resorption drugs that inhibit osteoclast-mediated bone resorption and change the bone metabolism. The effect of risedronate is 10 times stronger than that of alendronate, and 10.000 times stronger than that of etidronate. The bone turnover is reduced while the osteoblast activity and bone mineralisation are preserved. Decreases in biochemical markers of bone turnover were observed as soon as within 1 month and reached a maximum in 3-6 months of Actonel 35 mg application once a week or 5 mg a day. Several major international, randomised and placebo controlled clinical studies (VERT-NA, VERT-MN, HIP...) on more than 15,000 patients over 3-5 years of therapy have confirmed the speed, efficacy and excellent tolerability of risedronate in treating postmenopausal and corticosteroid-induced osteoporosis. After only 6 months of treatment VERT-NA and VERT-MN have shown a significant reduction in vertebral fracture risk versus control group, radiographically by 62% and clinically by 69% in the first year, which remains significant even after 5 years of treatment (50%) of postmenopausal osteoporosis. All the best properties of bisphosphonates have also been confirmed through a significant reduction in the relative risk of femoral neck fracture over 3 years of treatment by 40%, or by as much as 60% in female patients with osteoporosis and prevalent vertebral fracture, compared with controls. With risedronate we can achieve a quick and significant reduction in vertebral fracture risk in postmenopausal women (65%), especially among a high-risk population such as patients on long-term glucocorticoid therapy (70%) in the very first year of treatment. Prevention and treatment of glucocorticoid-induced osteoporosis is recommended in the administration of 27,5 mg of prednisone or prednisone equivalent in a duration longer than 3 months, irrespective of age or gender. Tolerability and safety of risedronate administration in osteoporosis is very good, almost the same as in the control group, although patients with earlier described or ongoing gastrointestinal troubles were also included. The incidence of endoscopically confirmed gastric ulcer in treatment with alendronate is significantly higher (13,2%) versus controls than in treatment with risedronate (4,1%). Risedronate is hence the first line of bisphosphonates for the reduction of vertebral and non-vertebral fracture risks in postmenopausal women with osteoporosis or those with a high risk of osteoporosis. It also efficiently prevents bone loss or improves bone density in men and women on a long-term corticosteroid therapy.
History of risedronate. [2021]Herein we review the discovery, development, commercial history and legacy of risedronate or NE-58095, a potent N-containing bisphosphonate developed by scientists at the Cincinnati Miami Valley Laboratories and the Norwich Eaton Laboratories of Procter and Gamble. It is characterized by a hydroxyl substituent (R1) and a pyridyl-methylene substituent (R2) at the carbon bridging two phosphonate moieties. It was shown to have greater potency than alendronate in cell-based systems while binding affinity to bone matrix was lower than alendronate, accounting for the relatively rapid offset of bone turnover inhibition when therapy is discontinued. Risedronate was shown to significantly reduce serum alkaline phosphatase and clinical features in patients with Paget's disease and was approved for this indication, at a dose of 30 mg daily for 2 months, in 1998. Formal dose response testing for treatment of osteoporosis was not performed. In large Phase 3 studies, 5 mg risedronate daily increased bone mineral density more than did the 2.5 mg dose. As a result, the 2.5 mg dose was dropped from most of the Phase 3 studies after 12 months. The 5 mg daily dose was approved for treating and preventing postmenopausal osteoporosis and glucocorticoid-induced osteoporosis in 2000. The drug was subsequently approved for treating men with osteoporosis. Following the leads of other companies, weekly and monthly preparations were developed and approved, based on non-inferiority BMD studies vs the 5 mg daily oral dose as was a unique dosing regimen of 75 mg given on 2 consecutive days each month. Finally, to overcome the effect of food on limiting the already poor gastrointestinal absorption of the drug, a once-weekly oral preparation containing the chelating agent EDTA and with an enteric coating delaying dissolution until the tablet was in the small intestine was approved in 2010 to be administered after breakfast. The Alliance for Better Bone Health, a collaboration between Procter & Gamble Pharmaceuticals and sanofi-aventis U.S. was formed to market risedronate as Actonel® and, subsequently, Actonel-EC® or Atelvia®. These drugs are still marketed by sanofi-aventis in some countries. The sale of the pharmaceutical division of Procter & Gamble to Warner Chilcott (US) was based, in large part, on the perceived value and marketability of the risedronate drugs. When marketing targets of Warner-Chilcott were not met, the rights of risedronate were sold to Allergan USA, Inc. which never actively promoted the drug. Generic forms of risedronate were introduced into the United States in 2015 but are rarely used, although several generic forms are actively marketed in other countries.
Review of risedronate in the treatment of osteoporosis. [2019]Risedronate (Actonel, Procter & Gamble and Aventis) is a novel, orally administered pyridinyl bisphosphonate. Preclinical studies have shown that risedronate is a potent inhibitor of osteoclasts. Risedronate inhibited bone resorption and increased bone density in the spine and hip. Prospective, randomised, placebo-controlled trials (RCTs) in patients with postmenopausal osteoporosis (PMO) have demonstrated that risedronate decreased the risk of vertebral fractures by up to 49% and of non-vertebral fractures by up to 39% over 3 years in postmenopausal women with one or more prevalent vertebral fractures. This reduction of the risk for vertebral fractures was significant from the first year of treatment (risk reduction up to 65%). Risedronate was the first bisphosphonate to be studied in a large RCT with prevention of hip fracture as the primary end point. In this study, risedronate reduced the risk of hip fracture by 40% in elderly women with low hip bone density and one clinical risk factor for hip fracture and by 60% in women with low bone density and a prevalent vertebral fracture at baseline. Risedronate was also effective in the prevention and treatment of bone loss in glucocorticoid-induced osteoporosis (GIO), with a positive effect on vertebral fractures within the first year. Risedronate was well-tolerated with a safety profile comparable to placebo in all clinical studies. Patients with a previous or current history of upper GI illness or who were taking NSAIDs or aspirin were not excluded from these studies. Importantly, the upper GI safety profile of risedronate was shown to be similar to that of placebo in endoscopic studies. There was no evidence of acute-phase reactions or primary mineralisation defects. The most appropriate dose of risedronate was 5 mg/day.
Bisphosphonate treatment of osteoporosis. [2022]Bisphosphonates represent the agents of choice for most patients with osteoporosis. They are the best studied of all agents for the prevention of bone loss and reduction in fractures. They increase BMD, primarily at the lumbar spine, but also at the proximal femur. In patients who have established osteoporosis, bisphosphonates reduce the risk of vertebral fractures, and are the only agents in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. Bisphosphonates reduce the risk of fracture quickly. The risk of radiographic vertebral deformities is reduced after 1 year of treatment with risedronate [68]. The risk of clinical vertebral fractures is reduced after 1 year of treatment with alendronate [69] and just 6 months' treatment with risedronate [157]. The antifracture effect of risedronate has been shown to continue through 5 years of treatment [158]. Alendronate and risedronate are approved by the FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for prevention (risedronate) and treatment (alendronate and risedronate) of glucocorticoid-induced osteoporosis. Alendronate is also approved for treatment of osteoporosis in men. Other bisphosphonates (etidronate for oral use, pamidronate and zoledronate for intravenous infusion) are also available and can be used off label for patients who cannot tolerate approved agents. Although bisphosphonates combined with estrogen or raloxifene produce greater gains in bone mass compared with single-agent treatment, the use of two antiresorptive agents in combination cannot be recommended because the benefit on fracture risk has not been demonstrated and because of increased cost and side effects.
Extemporaneous procedures for dissolving risedronate tablets for oral administration and for feeding tubes. [2018]Risedronate (Actonel, Procter & Gamble Pharmaceuticals) is commercially available only as film-coated tablets. Extemporaneous procedures for dissolving tablets for feeding tubes and for preparation of an oral liquid have not previously been evaluated.
Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. [2018]Bisphosphonates have been available for more than a decade. Currently, 4 bisphosphonates--alendronate, risedronate, ibandronate, and zoledronic acid--are approved in the United States. Alendronate and risedronate are oral agents, ibandronate is available in oral and intravenous formulations, and zoledronic acid is an intravenous drug. This review summarizes results from pivotal clinical trials in which these bisphosphonates have been shown to reduce risk for osteoporotic fractures. Also reviewed are results of "bridging" studies designed to demonstrate the comparable efficacy of less frequent dosing regimens to increase bone mineral density and to reduce bone turnover. Compared with placebo controls, all 4 approved bisphosphonates reduce the relative risk of new vertebral fractures in women with postmenopausal osteoporosis. Alendronate, risedronate, and zoledronic acid reduce the relative risk of new nonvertebral and hip fractures. Clinical trial extensions of up to 10 years with alendronate and 7 years with risedronate have shown that efficacy is maintained during long-term treatment.