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

Primary Purpose

Anorexia Nervosa

Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Denosumab subcutaneous injections
Placebo subcutaneous injections
Sponsored by
University Hospital, Montpellier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anorexia Nervosa

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • CHU Montpellier

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Denosumab subcutaneous injections

Placebo subcutaneous injections

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
values of bone mineral density at 24 months
Comparison of the levels of bone mineral density at 24 months
values of bone remodeling markers at 24 months
Comparison of the values of bone remodeling markers at 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).

Full Information

First Posted
October 1, 2015
Last Updated
January 3, 2019
Sponsor
University Hospital, Montpellier
Collaborators
University Hospital, Lille, Nantes University Hospital, University Hospital, Paris, University Hospital, Rouen
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1. Study Identification

Unique Protocol Identification Number
NCT02567279
Brief Title
Impact of Denosumab in the Prevention of Bone Loss in Non-menopausal Women With Anorexia Nervosa
Acronym
DIBLAN
Official Title
Impact of Denosumab in the Prevention of Bone Loss in Non-menopausal Women With Anorexia Nervosa
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Terminated
Why Stopped
Great difficulties were encountered during recruitment, for fear Denozumab. Only 2 patients have been included since the study start.
Study Start Date
June 1, 2016 (Actual)
Primary Completion Date
January 3, 2019 (Actual)
Study Completion Date
January 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Montpellier
Collaborators
University Hospital, Lille, Nantes University Hospital, University Hospital, Paris, University Hospital, Rouen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anorexia Nervosa

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Denosumab subcutaneous injections
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Placebo subcutaneous injections
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Denosumab subcutaneous injections
Other Intervention Name(s)
Treated group
Intervention Description
Subcutaneous injection of Denosumab 60 mg, one injection at baseline and another injection at 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo subcutaneous injections
Other Intervention Name(s)
Control group
Intervention Description
Subcutaneous injection of Placebo, one injection at baseline and another injection at 6 months
Primary Outcome Measure Information:
Title
Value of bone mineral density in lumbar spine (g/cm2)
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
value of bone mineral density in the whole body, the total proximal femur and the radius (g/cm2)
Description
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.
Time Frame
12 months
Title
values of bone mineral density at 24 months
Description
Comparison of the levels of bone mineral density at 24 months
Time Frame
24 months
Title
values of bone remodeling markers at 24 months
Description
Comparison of the values of bone remodeling markers at 24 months
Time Frame
24 months
Title
links between ESR1 genotype and bone minéral density at Baseline and response to Denosunab
Description
Assess the links between ESR1 genotype and BMD at baseline and response to Denosunab (variation of BMD between baseline and 12 months).
Time Frame
12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sébastien Guillaume, MD PhD
Organizational Affiliation
Hôpital Lapeyronie - CHU de Montpellier
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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