Effects of Denosumab on Bone Mineral Density, Markers of Bone Metabolism and Bone Microarchitecture in Women With Anorexia Nervosa: A Pilot Study
Overview
- Phase
- Phase 3
- Intervention
- Denosumab 60 MG [Prolia]
- Conditions
- Bone Density
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
This protocol is a randomized, double-blind, placebo-controlled clinical trial which aims to investigate the effect of denosumab on BMD in women with anorexia nervosa. The investigators hypothesize that 12 months of denosumab administration will result in an increase in bone mineral density, decrease in markers of bone resorption and improvement in bone microarchitecture in osteopenic women with anorexia nervosa compared with placebo.
An optional extension study will offer subjects 12-month administration of open-label alendronate (an oral bisphosphonate) after the initial 12 month administration of denosumab or placebo. We hypothesize that 12 months of denosumab followed by 12 months of open-label alendronate will result in a greater increase in BMD compared to 12 months of placebo followed by 12 months of open-label alendronate. Within the group of women who receive sequential therapy with 12 months of denosumab followed by 12 months of alendronate, we hypothesize that BMD will be maintained between 12 and 24 months while on alendronate.
Investigators
Karen Klahr Miller, MD
Professor of Medicine
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Age 20-60 years, skeletally mature with closed epiphyses
- •Anorexia nervosa or atypical anorexia nervosa defined by DSM-V diagnostic criteria
- •BMD T-score \< -1.0
- •Normal serum 25-OH vitamin D (\>30 ng/mL) and calcium levels
- •For women of reproductive age, agree to use an effective contraceptive method. Highly effective methods of birth control include:
- •Combined (estrogen and progestogen) hormonal methods (pills, vaginal ring, or skin patch)
- •Intrauterine device (IUD)
- •Intraduterine hormonal-releasing system (IUS)
- •Surgery to tie both fallopian tubes (bilateral tubal ligation/occlusion)
- •Your male partner has had a vasectomy and testing shows there is no sperm in the semen
Exclusion Criteria
- •Any disease known to affect bone, including untreated thyroid dysfunction, Cushing's or renal failure
- •Subjects with a known esophageal disease cannot participate in the alendronate extension study
- •Any medication known to affect bone metabolism within 3 months of the study, excluding oral contraceptives or other forms of estrogen administration. Bisphosphonates must have been discontinued for at least one year before participation
- •Immunodeficiency or taking immunosuppressive therapy
- •Serum potassium \<3.0 meq/L
- •Serum ALT \>3 times upper limit of normal
- •eGFR of less than 30 ml/min
- •Hypocalcemia
- •Diabetes mellitus
- •Active substance abuse, including alcohol
Arms & Interventions
Active Denosumab 60mg Injection
Denosumab 60mg injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Intervention: Denosumab 60 MG [Prolia]
Active Denosumab 60mg Injection
Denosumab 60mg injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Intervention: Alendronate 70Mg Tab
Placebo
Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Intervention: Placebo Injection
Placebo
Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
Intervention: Alendronate 70Mg Tab
Outcomes
Primary Outcomes
Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)
Time Frame: 12 months (Period 1)
Postero-anterior (PA) lumbar spine bone mineral density was assessed by dual-energy x-ray absorptiometry (DXA). The DXA scanner used was a Hologic Horizon A (Hologic, Inc., Waltham, MA).
Secondary Outcomes
- Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA(12 months to 24 months (Period 2))