Effects of Romosozumab on Bone Density in Women With Anorexia Nervosa

Effects of Romosozumab on Bone Density, Markers of Bone Metabolism and Bone Microarchitecture in Women With Anorexia Nervosa: A Pilot Study

This protocol is a randomized, double-blind, placebo-controlled clinical trial which aims to investigate the effect of romosozumab on BMD in women with anorexia nervosa. The investigators will also investigate the safety of romosozumab in women with anorexia nervosa. The investigators hypothesize that 12 months of romosozumab administration will result in an increase in bone mineral density, increase in markers of bone formation and decrease in markers of bone resorption, and improvement in bone microarchitecture in osteopenic women with anorexia nervosa compared with placebo.

The extension study will offer subjects 12-month administration of open-label alendronate (an oral bisphosphonate) 70 mg once weekly after the initial 12 month administration of romosozumab or placebo. The investigators hypothesize that 12 months of romosozumab 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 romosozumab followed by 12 months of alendronate, the investigators hypothesize that BMD will be maintained between 12 and 24 months while on alendronate.

Study Overview

• Status: Active, not recruiting
• Conditions: Anorexia Nervosa; Bone Loss; Eating Disorders; Bone Density, Low
• Intervention / Treatment: Drug: Romosozumab Prefilled Syringe; Drug: Alendronate 70Mg Tab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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), intrauterine hormonal-releasing system (IUS), surgery to tie both fallopian tubes (bilateral tubal ligation/occlusion), and woman's 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:

• Body mass index (BMI) <17 kg/m2
• Hospitalization within 3 months of baseline study visit, including inpatient eating disorder treatment facility; participating in a residential eating disorder treatment program within 3 months of study participation is permitted
• Myocardial infarction or stroke within 1 year preceding enrollment
• Any disease known to affect bone, including untreated thyroid dysfunction, Cushing's or renal failure
• 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 25-OH vitamin D level <30 ng/mL
• Serum potassium <3.0 meq/L
• Serum magnesium <1.5 meq/L
• Serum ALT >3 times upper limit of normal
• eGFR of less than 30 ml/min
• LDL > 190 mg/dL
• 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 sensitivity to any of the products or components of the medication to be administered
• Sensitivity to calcium or vitamin D supplements
• Pregnant, planning to become pregnant within 7 months after the end of treatment, and/or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Romosozumab 210mg Injection; Romosozumab 210mg injection monthly for 12 months. Alendronate 70mg PO weekly starting at Month 12 through 24 months.	Drug: Romosozumab Prefilled Syringe; Romosozumab 210mg Injection monthly for 12 months; Drug: Alendronate 70Mg Tab; Alendronate 70mg PO weekly starting at 12 months through 24 months.
Placebo Comparator: Placebo; Placebo injection monthly for 12 months. Alendronate 70mg PO weekly starting at Month 12 through 24 months.	Drug: Alendronate 70Mg Tab; Alendronate 70mg PO weekly starting at 12 months through 24 months.; Drug: Placebo; Placebo Injection monthly for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bone density	Change in bone density	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bone density	Change in bone density	6 months, 24 months

Collaborators and Investigators

• Sponsor: Karen Klahr Miller, MD
• Collaborators: Amgen

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: February 26, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Signs and Symptoms, Digestive; Musculoskeletal Diseases; Bone Diseases; Anorexia; Anorexia Nervosa; Feeding and Eating Disorders; Bone Diseases, Metabolic; Physiological Effects of Drugs; Bone Density Conservation Agents; Alendronate
• Other Study ID Numbers: 2020P000329

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No