Anorexia NervosaPhase 1PRE-GAiNNCT04021017
PRE-GAiN Bone Health Pilot Study
A Phase 1 study testing Estradiol Hemihydrate Transdermal System in people with Anorexia Nervosa, run by University of Saskatchewan at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 12 to 19 years, women only
- Conditions the study is for
- Anorexia Nervosa
- What is being tested?
- Estradiol Hemihydrate Transdermal System
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- 21 Jan 2020to 13 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 19 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PRE-GAIN Bone Health Pilot Study - Physiologic Replacement of EstroGen for Adolescent Females With AnorexIa Nervosa for Bone Health Pilot Study
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.
Read the 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).
- Conditions
- Anorexia Nervosa
- Being tested
- Estradiol Hemihydrate Transdermal System
- Keywords
- estrogen, anorexia, bone health, bone accrual, IGF-1
- Medical subject headings
- Anorexia Nervosa, Anorexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol Hemihydrate Transdermal SystemDrug
Also called PrClimara® 25
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Estradiol Hemihydrate Transdermal System |
| No Treatment | No intervention | The participants in this group will not receive the estrogen patch nor the oral progesterone. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cortical Wall Thickness
Cortical wall thickness as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Measured: Change from Baseline to Month 24
Secondary outcomes (5)
Areal Bone Content
Areal bone content as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Measured: Change from Baseline to Month 24
Bone Micro-architectural Parameters
Bone micro-architectural parameters as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Measured: Change from Baseline to Month 24
Volumetric Bone Density
Volumetric bone density as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Measured: Change from Baseline to Month 24
Bone Strength Estimates
Bone strength estimates as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Measured: Change from Baseline to Month 24
Vertebral Fracture Rates
Vertebral fracture rates as measured by lateral spine x-ray
Measured: Change from Baseline to Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2019
- Study start21 Jan 2020
- Primary completion13 Dec 2022
- Study completion13 Dec 2022
Why it stopped: PI Workload
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anorexia NervosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Saskatchewan
- Sponsor type
- University, hospital or other
- Collaborators
- Jim Pattison Children's Hospital Foundation
- Responsible party
- Principal investigator, Munier Nour, University of Saskatchewan
- Investigators
- Munier Nour, Principal investigator, Faculty
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04021017
- Sponsor's protocol ID
- PRE-GAiN-01
- Acronym
- PRE-GAiN
- Status last verified
- Dec 2022
- First submitted
- 12 Jul 2019
- Last updated
- 16 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRE-GAIN Bone Health Pilot Study - Physiologic Replacement of EstroGen for Adolescent Females With AnorexIa Nervosa for Bone Health Pilot Study
- ClinicalTrials.gov ID
- NCT04021017
- Acronym / sponsor ID
- PRE-GAiN / PRE-GAiN-01
- Conditions
- Anorexia Nervosa
- Keywords
- estrogen, anorexia, bone health, bone accrual, IGF-1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI Workload
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of SaskatchewanUniversity, hospital or other
- Collaborators
- Jim Pattison Children's Hospital Foundation
- Study start
- 21 Jan 2020 (actual)
- Primary completion
- 13 Dec 2022 (actual)
- Study completion
- 13 Dec 2022 (actual)
- First posted
- 16 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Estradiol Hemihydrate Transdermal SystemParticipants 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. |
| No Treatment | No intervention | –The participants in this group will not receive the estrogen patch nor the oral progesterone. |
Who may qualify
- Ages
- 12 to 19 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (19 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Estradiol Hemihydrate Transdermal SystemAlso: PrClimara® 25Participants 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. | Drug | Treatment |
Primary outcome
Cortical Wall Thickness
Time frame: Change from Baseline to Month 24
Cortical wall thickness as measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
5 secondary outcomes
Areal Bone Content
Time frame: Change from Baseline to Month 24
Bone Micro-architectural Parameters
Time frame: Change from Baseline to Month 24
Volumetric Bone Density
Time frame: Change from Baseline to Month 24
Bone Strength Estimates
Time frame: Change from Baseline to Month 24
Vertebral Fracture Rates
Time frame: Change from Baseline to Month 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Munier Nour principal investigator
Faculty
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Estradiol Hemihydrate Transdermal System in people with Anorexia Nervosa, run by University of Saskatchewan at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortical Wall Thickness (time frame: Change from Baseline to Month 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2022.