search
Back to results

PRE-GAiN Bone Health Pilot Study (PRE-GAiN)

Primary Purpose

Anorexia Nervosa

Status
Withdrawn
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Estradiol Hemihydrate Transdermal System
Sponsored by
University of Saskatchewan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anorexia Nervosa focused on measuring estrogen, anorexia, bone health, bone accrual, IGF-1

Eligibility Criteria

12 Years - 19 Years (Child, Adult)FemaleDoes not accept healthy volunteers

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)

Sites / Locations

  • Royal University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treatment

No Treatment

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Areal Bone Content
Areal bone content as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Bone Micro-architectural Parameters
Bone micro-architectural parameters as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Volumetric Bone Density
Volumetric bone density as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Bone Strength Estimates
Bone strength estimates as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Vertebral Fracture Rates
Vertebral fracture rates as measured by lateral spine x-ray

Full Information

First Posted
July 12, 2019
Last Updated
December 14, 2022
Sponsor
University of Saskatchewan
Collaborators
Jim Pattison Children's Hospital Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT04021017
Brief Title
PRE-GAiN Bone Health Pilot Study
Acronym
PRE-GAiN
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Withdrawn
Why Stopped
PI Workload
Study Start Date
January 21, 2020 (Actual)
Primary Completion Date
December 13, 2022 (Actual)
Study Completion Date
December 13, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Saskatchewan
Collaborators
Jim Pattison Children's Hospital Foundation

4. Oversight

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
Data Monitoring Committee
No

5. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anorexia Nervosa
Keywords
estrogen, anorexia, bone health, bone accrual, IGF-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
No Treatment
Arm Type
No Intervention
Arm Description
The participants in this group will not receive the estrogen patch nor the oral progesterone.
Intervention Type
Drug
Intervention Name(s)
Estradiol Hemihydrate Transdermal System
Other Intervention Name(s)
PrClimara® 25
Intervention Description
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.
Primary Outcome Measure Information:
Title
Cortical Wall Thickness
Description
Cortical wall thickness as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Time Frame
Change from Baseline to Month 24
Secondary Outcome Measure Information:
Title
Areal Bone Content
Description
Areal bone content as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Time Frame
Change from Baseline to Month 24
Title
Bone Micro-architectural Parameters
Description
Bone micro-architectural parameters as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Time Frame
Change from Baseline to Month 24
Title
Volumetric Bone Density
Description
Volumetric bone density as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Time Frame
Change from Baseline to Month 24
Title
Bone Strength Estimates
Description
Bone strength estimates as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Time Frame
Change from Baseline to Month 24
Title
Vertebral Fracture Rates
Description
Vertebral fracture rates as measured by lateral spine x-ray
Time Frame
Change from Baseline to Month 24

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Munier Nour
Organizational Affiliation
Faculty
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal University Hospital
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 0W8
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

PRE-GAiN Bone Health Pilot Study

We'll reach out to this number within 24 hrs