Clinical trial NCT04021017: PRE-GAiN Bone Health Pilot Study
Official title: PRE-GAIN Bone Health Pilot Study - Physiologic Replacement of EstroGen for Adolescent Females With AnorexIa Nervosa for Bone Health Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Anorexia Nervosa
Keywords: estrogen
anorexia
bone health
bone accrual
IGF-1
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
Collaborators: name: Jim Pattison Children's Hospital Foundation
First posted: 2019-07-16
Enrollment: 0
Sex: FEMALE
Minimum age (years): 12
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants in this study will be randomized 1:1 into 2 groups. One group will receive treatment with a transdermal estrogen patch and the other group will not.
Primary purpose: TREATMENT

Brief summary: This study will assess the affects of an estradiol hemihydrate transdermal system on bone health in 24 adolescent females aged 12-19 years old with anorexia nervosa. Participants in this study will be randomized 1:1 into 2 groups. One group will receive treatment with a transdermal estrogen patch and the other group will not.

Detailed description: Currently, no therapy exists to improve bone health in females with anorexia nervosa (AN) other than improving body mass. Transdermal estrogen is being investigated as to whether it has benefit to bone health parameters.

While numerous studies have sought to orally replace estrogen in adolescents and women with AN, the replacement therapy suppresses IGF-1, and as a result oral estrogen studies have demonstrated no bone health benefit in AN. However, transdermal physiologic estrogen, due to no first-pass metabolism in the liver, is not IGF-1 suppressive. IGF-1 is known to be hormone that directly affects bone formation and is considered to be osteoanabolic (helps increase bone mass).

Eligibility criteria: Inclusion Criteria:

* Female
* Age 12 - 19 years old
* Meet DSM-5 criteria for Anorexia Nervosa

  o Criteria includes: persistent restriction of energy intake leading to significantly low body weight; either an intense fear of gaining weight or persistent behavior that interferes with weight gain; and a disturbance in the way one's body weight or shape is experienced
* Amenorrhea for at least three months

  * Amenorrhea is a required inclusion criteria as participants with intact menstruation do not meet justification for estrogen replacement (as they are not estrogen deficient)
  * Participants will have been seen and assessed by anorexia clinic physician prior to enrollment to exclude and treat other causes of amenorrhea
* Agree to use a highly effective contraceptive method for the duration of study therapy.

Exclusion Criteria:

* Uncontrolled or chronic medical conditions that may influence bone health (i.e. hyperthyroidism, diabetes mellitus, or celiac disease)
* Use of supraphysiologic corticosteroids for greater than three months
* Pregnancy or attempting pregnancy
* Cigarette smoker
* Known history of a blood clotting disorder (i.e. Factor V Leiden, Protein C Deficiency, etc.)
* Known predisposition to estrogen-related cancers, such as breast or ovarian cancer (e.g. BRCA1)
* Hypersensitivity to this drug or to any ingredient in the formulation or component of the container
* Liver dysfunction or disease as long as liver function tests have failed to return to normal
* Known or suspected estrogen-dependent malignant neoplasia (e.g. endometrial cancer)
* Endometrial hyperplasia
* Known, suspected, or past history of breast cancer
* Undiagnosed abnormal genital bleeding
* Known or suspected pregnancy or lactation
* Active or past history of arterial thromboembolic disease (e.g. stroke, myocardial infarction, coronary heart disease)
* Active or past history of confirmed venous thromboembolism (such as deep vein thrombosis or pulmonary embolism) or active thrombophlebitis
* A high risk of venous or arterial thrombosis, including known thrombophilic disorders
* Partial or complete loss of vision due to ophthalmic vascular disease
* Presence or history of liver tumours (benign or malignant)
* Ongoing use of estrogen containing contraception (oral birth control pill, vaginal ring, patches, depo injections)

Primary outcomes:
measure: Cortical Wall Thickness
timeFrame: Change from Baseline to Month 24
Secondary outcomes:
measure: Areal Bone Content
timeFrame: Change from Baseline to Month 24
measure: Bone Micro-architectural Parameters
timeFrame: Change from Baseline to Month 24
measure: Volumetric Bone Density
timeFrame: Change from Baseline to Month 24
measure: Bone Strength Estimates
timeFrame: Change from Baseline to Month 24
measure: Vertebral Fracture Rates
timeFrame: Change from Baseline to Month 24
Other outcomes:
Locations:
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
Study officials:
affiliation: Faculty
name: Munier Nour
role: PRINCIPAL_INVESTIGATOR
References: