Clinical trial NCT03292146: Effects of Denosumab on Bone Mineral Density in Women With Anorexia Nervosa: A Pilot Study
Official title: Effects of Denosumab on Bone Mineral Density, Markers of Bone Metabolism and Bone Microarchitecture in Women With Anorexia Nervosa: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Density
Bone Loss
Anorexia Nervosa
Eating Disorder
Atypical Anorexia Nervosa
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2017-09-25
Enrollment: 30
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion/Exclusion 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

Primary outcomes:
measure: Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)
timeFrame: 12 months (Period 1)
Secondary outcomes:
measure: Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA
timeFrame: Baseline to 24 months
measure: Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA
timeFrame: 12 months to 24 months (Period 2)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Karen K Miller, MD
role: PRINCIPAL_INVESTIGATOR
References: