Impact of Denosumab in the Prevention of Bone Loss in Non-menopausal Women With Anorexia Nervosa (DIBLAN)

The drastic reduction of nutritional intake in anorexia nervosa(AN) alters many hormonal factors that regulate the activity of bone cells. This alteration of bone remodeling is characterized by increased bone resorption and decreased bone formation, leading to a marked reduction of bone mineral density, osteoporosis and an increased risk of fracture.

To date, there is a paucity of studies and no consensus on the management of bone loss in patients with AN. The few previous studies were performed with small samples and using short follow-up periods.

Denosumab is a fully human monoclonal antibody that binds with high specificity to human RANKL (6, 7), thereby reducing the number and activity of osteoclasts and therefore decreasing bone resorption that was found increased in patients AN.

Denosumab may transiently protect bone whilst psychonutritional management will induce a weight restoration

Study Overview

• Status: Terminated
• Conditions: Anorexia Nervosa
• Intervention / Treatment: Drug: Denosumab subcutaneous injections; Drug: Placebo subcutaneous injections

Detailed Description

The project propose to assess, with a double-blind multicentric randomized clinical trial, the effects of Denosumab on bone mineral density (BMD) change at lumbar spine over 12 months among patients suffering from an acute anorexia nervosa (AN).

84 patients suffering from a current anorexia nervosa with an evidence of low BMD determined by a Z-score value < -2 DS at least one site (lumbar spine or total proximal femur) will be recruit .

Eligible patients will be randomized into two groups: denosumab versus placebo. Each patient will attend a total of 8 scheduled visits, which will be completed over a period of 24 months +/- 15days from screening visit to end of study (inclusion, 10 days, and 3, 6, 12, 15, 18, & 24 months).

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • CHU Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

• Patients with a current AN defined by DSM-V criteria
• Being female

• Age over or equal to 18 years and less or equal to 40 years

  . For patients under 20 years of age, effective bone maturation (attested by a radiography of the hip)

• Agree to take contraception up to five months after the last injection of denosumab .
• Absence of pregnancy evidenced by an interview and a negative assay of human chorionic gonadotropin (ßhCG).
• Evidence of low BMD determined by Z-score value < -2 DS (at least one site (lumbar spine or total proximal femur)
• Signing an informed consent.

Exclusion criteria:

• Not affiliated to a social security scheme or not being the beneficiary of such a scheme.
• Severe hepatic cytolysis with transaminase up to 5 times normal.
• Severe dental problems: in case of doubt an assessment by a dentist will be required before inclusion.
• Desire of pregnancy during the two years of follow-up study.
• Disease or treatment potentially responsible for secondary osteoporosis.
• Participant already treated with a molecule known to have an effect on bone
• Diabetes.
• Current hypocalcemia.
• Immunodeficiency.
• Cancer with bone lesions
• Patient on protectice measures (guardianship or trusteeship)
• Hypersensitivity to the active substance or to any of the excipients of Prolia®
• Unable to read and / or write and understand the methodology of the study
• Reporting relationship to the investigator
• Anticipate a long stay outside the region that would prevent compliance with the schedule of visits
• Participation to other biomedical research on health products
• Deprived of liberty
• Breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Denosumab subcutaneous injections; The treated group (n = 42) will receive Denosumab (60 mg, two subcutaneous injections at M0 and M6) associated with a daily treatment of vitamin D (800 IU) + calcium (1000 mg).	Drug: Denosumab subcutaneous injections; Subcutaneous injection of Denosumab 60 mg, one injection at baseline and another injection at 6 months; Other Names: Treated group
Placebo Comparator: Placebo subcutaneous injections; The control group (n = 42) will received a placebo injection (two subcutaneous injections at M0 and M6) with daily treatment of vitamin D (800 IU) +calcium (1000 mg).	Drug: Placebo subcutaneous injections; Subcutaneous injection of Placebo, one injection at baseline and another injection at 6 months; Other Names: Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Value of bone mineral density in lumbar spine (g/cm2)	Comparison of bone mineral density changes in the lumbar spine at M12 between groups with Denosumab and placebo after two injections either of Denosumab or placebo. Bone mineral density is objectified by the Z-score obtained by bone mineral density.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
value of bone mineral density in the whole body, the total proximal femur and the radius (g/cm2)	Comparison of bone mineral density changes in the whole body, the total proximal femur and the radius between groups at M12 after two injections of Denosumab.	12 months
values of bone mineral density at 24 months	Comparison of the levels of bone mineral density at 24 months	24 months
values of bone remodeling markers at 24 months	Comparison of the values of bone remodeling markers at 24 months	24 months
links between ESR1 genotype and bone minéral density at Baseline and response to Denosunab	Assess the links between ESR1 genotype and BMD at baseline and response to Denosunab (variation of BMD between baseline and 12 months).	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: University Hospital, Rouen; University Hospital, Lille; Nantes University Hospital; University Hospital, Paris
• Investigators: Principal Investigator: Sébastien Guillaume, MD PhD, Hôpital Lapeyronie - CHU de Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): January 3, 2019
• Study Completion (Actual): January 3, 2019

Study Registration Dates

• First Submitted: October 1, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): January 7, 2019
• Last Update Submitted That Met QC Criteria: January 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Anorexia; Anorexia Nervosa; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 9531

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No