PRE-GAiN Bone Health Pilot Study

NCT ID: NCT04021017

Last Updated: 2022-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-21

Study Completion Date

2022-12-13

Brief Summary

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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

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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).

Conditions

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Anorexia Nervosa

Keywords

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estrogen anorexia bone health bone accrual IGF-1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment

Participants randomized to the treatment arm will be divided by maturational status:

* Participants who have had their first period or have a bone age greater than or equal to 14 years will receive PrClimara® 25 (estradiol hemihydrate transdermal system - 25 mcg/day) as a weekly patch, for 24 months.

o These participants will also receive progesterone (Provera 10 mg tablet) orally every 4 weeks, for 7 days during the second half of the planned menstrual cycle, in order to induce a menstrual period.
* Participants who have not yet had their first period and have a bone age below 14 years will receive an increasing dose of estrogen. These participants will be initiated on graduated dose of transdermal 17-β estradiol patches:

* 3.1 mcg/day (1/8 patch) for first six-months,
* 6.2 mcg/day (1/4 patch) for second six-months,
* 12.5 mcg/day (1/2 patch) for third six-months, and
* 25 mcg/day (full patch) for final six-months.

Group Type EXPERIMENTAL

Estradiol Hemihydrate Transdermal System

Intervention Type DRUG

Participants who have had their first period or have a bone age greater than or equal to 14 years will receive PrClimara® 25 (estradiol hemihydrate transdermal system - 25 mcg/day) as a weekly patch, for 24 months. Participants who have not yet had their first period and have a bone age below 14 years will receive an increasing dose of estrogen. These participants will be initiated on graduated dose of transdermal 17-β estradiol patches: 3.1 mcg/day (1/8 patch) for first six-months, 6.2 mcg/day (1/4 patch) for second six-months, 12.5 mcg/day (1/2 patch) for third six-months and 25 mcg/day (full patch) for final six-months.

No Treatment

The participants in this group will not receive the estrogen patch nor the oral progesterone.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Estradiol Hemihydrate Transdermal System

Participants who have had their first period or have a bone age greater than or equal to 14 years will receive PrClimara® 25 (estradiol hemihydrate transdermal system - 25 mcg/day) as a weekly patch, for 24 months. Participants who have not yet had their first period and have a bone age below 14 years will receive an increasing dose of estrogen. These participants will be initiated on graduated dose of transdermal 17-β estradiol patches: 3.1 mcg/day (1/8 patch) for first six-months, 6.2 mcg/day (1/4 patch) for second six-months, 12.5 mcg/day (1/2 patch) for third six-months and 25 mcg/day (full patch) for final six-months.

Intervention Type DRUG

Other Intervention Names

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PrClimara® 25

Eligibility Criteria

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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

* 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)
Minimum Eligible Age

12 Years

Maximum Eligible Age

19 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Jim Pattison Children's Hospital Foundation

UNKNOWN

Sponsor Role collaborator

University of Saskatchewan

OTHER

Sponsor Role lead

Responsible Party

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Munier Nour

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Munier Nour

Role: PRINCIPAL_INVESTIGATOR

Faculty

Locations

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Royal University Hospital

Saskatoon, Saskatchewan, Canada

Site Status

Countries

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Canada

Other Identifiers

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PRE-GAiN-01

Identifier Type: -

Identifier Source: org_study_id