PRE-GAiN Bone Health Pilot Study

Anorexia Nervosa Clinical Trial

— 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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04021017
• Other study ID #: PRE-GAiN-01
• Status: Withdrawn
• Phase: Phase 1
• Start date: January 21, 2020
• Est. completion date: December 13, 2022

Study information

• Verified date: December 2022
• Source: University of Saskatchewan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 13, 2022
• Est. primary completion date: December 13, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 12 Years to 19 Years

Eligibility

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)

Related Conditions & MeSH terms

• Anorexia
• Anorexia Nervosa

Intervention

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-ß 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.

Locations

Country	Name	City	State
Canada	Royal University Hospital	Saskatoon	Saskatchewan

Sponsors (2)

Lead Sponsor	Collaborator
University of Saskatchewan	Jim Pattison Children's Hospital Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cortical Wall Thickness	Cortical wall thickness as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).	Change from Baseline to Month 24
Secondary	Areal Bone Content	Areal bone content as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).	Change from Baseline to Month 24
Secondary	Bone Micro-architectural Parameters	Bone micro-architectural parameters as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).	Change from Baseline to Month 24
Secondary	Volumetric Bone Density	Volumetric bone density as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).	Change from Baseline to Month 24
Secondary	Bone Strength Estimates	Bone strength estimates as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).	Change from Baseline to Month 24
Secondary	Vertebral Fracture Rates	Vertebral fracture rates as measured by lateral spine x-ray	Change from Baseline to Month 24