PRE-GAiN Bone Health Pilot Study

Sponsor
University of Saskatchewan (Other)
Overall Status
Recruiting
CT.gov ID
NCT04021017
Collaborator
Jim Pattison Children's Hospital Foundation (Other)
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Estradiol Hemihydrate Transdermal System
Phase 1

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
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.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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
PRE-GAIN Bone Health Pilot Study - Physiologic Replacement of EstroGen for Adolescent Females With AnorexIa Nervosa for Bone Health Pilot Study
Actual Study Start Date :
Jan 21, 2020
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: 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.
Other Names:
  • PrClimara® 25
  • No Intervention: No Treatment

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

    Outcome Measures

    Primary Outcome Measures

    1. Cortical Wall Thickness [Change from Baseline to Month 24]

      Cortical wall thickness as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).

    Secondary Outcome Measures

    1. Areal Bone Content [Change from Baseline to Month 24]

      Areal bone content as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).

    2. Bone Micro-architectural Parameters [Change from Baseline to Month 24]

      Bone micro-architectural parameters as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).

    3. Volumetric Bone Density [Change from Baseline to Month 24]

      Volumetric bone density as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).

    4. Bone Strength Estimates [Change from Baseline to Month 24]

      Bone strength estimates as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).

    5. Vertebral Fracture Rates [Change from Baseline to Month 24]

      Vertebral fracture rates as measured by lateral spine x-ray

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 19 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Royal University Hospital Saskatoon Saskatchewan Canada S7N 0W8

    Sponsors and Collaborators

    • University of Saskatchewan
    • Jim Pattison Children's Hospital Foundation

    Investigators

    • Principal Investigator: Munier Nour, Faculty

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Munier Nour, Principal Investigator, University of Saskatchewan
    ClinicalTrials.gov Identifier:
    NCT04021017
    Other Study ID Numbers:
    • PRE-GAiN-01
    First Posted:
    Jul 16, 2019
    Last Update Posted:
    May 17, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Munier Nour, Principal Investigator, University of Saskatchewan
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 17, 2021