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

NCT02567279 | Terminated Phase 3 DMC

• 1 other identifier: 9531
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Anorexia Nervosa

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• value of bone mineral density in the whole body, the total proximal femur and the radius (g/cm2)

  12 months

• values of bone mineral density at 24 months

  24 months

• values of bone remodeling markers at 24 months

  24 months

• links between ESR1 genotype and bone minéral density at Baseline and response to Denosunab

  12 months

Study Arms (2)

Denosumab subcutaneous injections

ACTIVE COMPARATOR

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

Placebo subcutaneous injections

PLACEBO COMPARATOR

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

Interventions

Denosumab subcutaneous injections DRUG

Subcutaneous injection of Denosumab 60 mg, one injection at baseline and another injection at 6 months

Also known as: Treated group

Denosumab subcutaneous injections

Placebo subcutaneous injections DRUG

Subcutaneous injection of Placebo, one injection at baseline and another injection at 6 months

Also known as: Control group

Placebo subcutaneous injections

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• University Hospital, Lille: collaborator
• Nantes University Hospital: collaborator
• University Hospital, Paris: collaborator
• University Hospital, Rouen: collaborator

Study Sites (1)

CHU Montpellier

Montpellier, 34295, France

Location

MeSH Terms

Conditions

Anorexia Nervosa

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Sébastien Guillaume, MD PhD

  Hôpital Lapeyronie - CHU de Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2015
• First Posted: October 2, 2015
• Study Start: June 1, 2016
• Primary Completion: January 3, 2019
• Study Completion: January 3, 2019
• Last Updated: January 7, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)