Effects of Denosumab on Bone Mineral Density in Women With Anorexia Nervosa: A Pilot Study

NCT ID: NCT03292146

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-25
• Study Completion Date: 2021-07-22

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.

Conditions

Bone Density; Bone Loss; Anorexia Nervosa; Eating Disorder; Atypical Anorexia Nervosa

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Denosumab 60 MG [Prolia]

Intervention Type: DRUG

Denosumab 60mg injection at baseline and 6 months

Alendronate 70Mg Tab

Intervention Type: DRUG

Alendronate 70mg PO weekly starting at Month 12 through 24 months.

Placebo

Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.

Group Type: PLACEBO_COMPARATOR

Placebo Injection

Intervention Type: DRUG

Placebo Injection at baseline and 6 months

Alendronate 70Mg Tab

Intervention Type: DRUG

Alendronate 70mg PO weekly starting at Month 12 through 24 months.

Interventions

Denosumab 60 MG [Prolia]

Denosumab 60mg injection at baseline and 6 months

Intervention Type: DRUG

Placebo Injection

Placebo Injection at baseline and 6 months

Intervention Type: DRUG

Alendronate 70Mg Tab

Alendronate 70mg PO weekly starting at Month 12 through 24 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female
• 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
• Dental check up within the past year

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
• History of malignancy
• Paget disease of bone
• Osteomalacia
• Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (eg, tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal and/or pre-existing dental disease, and current use of corticosteroids.
• Planned invasive dental procedure over the next 24 months.
• Known senstivity to any of the products or components to be administered during dosing or known sensitivity to mammalian cell derived drug products
• Sensitivity to calcium or vitamin D supplements
• Pregnant, planning to become pregnant with 7 months after the end of treatment and/or breastfeeding

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Karen Klahr Miller, MD

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karen K Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017P000529

Identifier Type: -

Identifier Source: org_study_id