PRE-GAiN Bone Health Pilot Study

NCT04021017 | Withdrawn Phase 1

• 1 other identifier: PRE-GAiN-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Anorexia Nervosa

Keywords

estrogen; anorexia; bone health; bone accrual; IGF-1

Outcome Measures

Primary Outcomes (1)

• Cortical Wall Thickness

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

  Change from Baseline to Month 24

Secondary Outcomes (5)

• Areal Bone Content

  Change from Baseline to Month 24

• Bone Micro-architectural Parameters

  Change from Baseline to Month 24

• Volumetric Bone Density

  Change from Baseline to Month 24

• Bone Strength Estimates

  Change from Baseline to Month 24

• Vertebral Fracture Rates

  Change from Baseline to Month 24

Study Arms (2)

Treatment

EXPERIMENTAL

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

No Treatment

NO INTERVENTION

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

Interventions

Estradiol Hemihydrate Transdermal System 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.

Also known as: PrClimara® 25

Treatment

Eligibility Criteria

• Age: 12 Years - 19 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Saskatchewan: lead
• Jim Pattison Children's Hospital Foundation: collaborator

Study Sites (1)

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

MeSH Terms

Conditions

Anorexia Nervosa; Anorexia

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Munier Nour

  Faculty

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: July 16, 2019
• Study Start: January 21, 2020
• Primary Completion: December 13, 2022
• Study Completion: December 13, 2022
• Last Updated: December 16, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)