Role of Estrogen on Skeletal Outcomes in FHA
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age14-30
SponsorUniversity of Virginia
About this trial
The purpose of this study is to assess whether the natural form of estrogen (17-beta estradiol) given as a patch so that it is absorbed through your skin, is better at improving bone strength over 1 year than natural estrogen (17-beta estradiol) taken by mouth, or a synthetic form oestrogen (ethinyl estradiol) given as a patch that also provides birth control.
Participants will:
1. Take estrogen for 1 year either (i) in its natural form as a patch twice a week (and progesterone by mouth for 12 days of each month), or (ii) in its natural form as a pill daily (and progesterone by mouth for 12 days of each month), or (iii) in a synthetic form as a birth control patch weekly for 3 weeks with 1 week off the patch. You will not be able to choose which form of estrogen you will receive as this will be assigned to you based on a pre-existing randomization sequence (like the flip of a coin) 2. Take provided calcium and vitamin D supplements 3. Attend 4 study visits over 12 months with two at the beginning and then every 6 months that include:
* History and Physical Exams * Lab Work * Imaging studies * Questionnaires * Dietary recalls
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Females, age 14-30 years, skeletally mature with bone age ≥ 14 years (only 2% of growth left)
Women of reproductive age: use of an effective non-hormonal contraceptive method or a progestin releasing intrauterine device (no systemic skeletal effects) for study duration if sexually active. Note: Women who receive a progestin implant for contraception after study enrollment will be allowed to continue and will not be excluded from study.
Biochemical criteria: negative βHCG (pregnancy test), TSH within 2x the upper limit of normal, prolactin <10 ng/mL above upper limit of normal, potassium between 3.0-5.0, ALT ≤3 times upper limit of normal, LDL ≤190 mg/dl.
Patients with known hypothyroidism will be included if appropriately treated with levothyroxine and have a TSH within 2x the upper limit of normal for at least a month preceding the baseline study visit.
Disqualifiers
Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus
Primary thyroid dysfunction will be defined as a TSH level more than 2X the upper limit of normal per given reference range with unknown thyroid antibody status, or an abnormal TSH if known positive antibodies.
Patients with hypothyroidism will be excluded if not appropriately treated with levothyroxine and if they do not have a TSH level within 2X the upper limit of normal for at least a month preceding the baseline study visit, given possible effects on the reproductive axis and bone.
Use of other medications known to affect bone metabolism within 3 months of the study (other than calcium and vitamin D supplementation)
Trial design
Design model
Parallel
Treatments tested in this trial
transdermal 17β-E2 with cyclic progestin
Drug100-mcg transdermal 17β-E2 patch (to be applied twice weekly) (continuous use), with 200 mg micronized progesterone given for 12 days of every month
oral 17β-E2 with cyclic progestin
Drug2 mg of oral 17β-E2 pills daily, with 200 mg micronized progesterone given for 12 days of every month
transdermal EE+LNG
Drugtransdermal EE (30 mcg) + LNG (120 mcg) contraceptive patch (TWIRLA). Patch will be applied once a week for 3 consecutive weeks, with the 4th week off the patch (to be repeated after 4 weeks).
Treatment groups
150 Participants
are divided into 3 treatment groupsGroup A: transdermal 17β-E2 with cyclic progestinExperimental treatment 1 intervention
Group B: oral 17β-E2 with cyclic progestinExperimental treatment 1 intervention
Group C: transdermal EE+LNGExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Areal BMD at the spine, hip and femoral neck as well as spine trabecular bone score from DXA
Using repeated measures analysis, the investigators will compare change in lumbar spine, total hip and femoral neck BMD and trabecular bone score after 12 months of treatment between the transdermal 17β-E2 group and each of the oral 17β-E2 and transdermal EE+LNG groups. BMD and TBS are assessed using DXA. Unit for BMD is g/cm2.
Time frame
Baseline and post-treatment (12 months)2
12-month change in volumetric BMD at the radius and tibia
Using repeated measures analysis, the investigators will compare change in volumetric BMD at the radius and tibia after 12 months of treatment between the transdermal 17β-E2 group and each of the oral 17β-E2 and transdermal EE+LNG groups. Volumetric BMD is assessed using HRpQCT (mgHA/cm3)
Time frame
Baseline and post- treatment (12 months)3
12-month change in cortical thickness at the radius and tibia
Using repeated measures analysis, the investigators will compare change in cortical thickness at the radius and tibia after 12 months of treatment between the transdermal 17β-E2 group and each of the oral 17β-E2 and transdermal EE+LNG groups. Cortical thickness is assessed using HRpQCT (mm).
Time frame
Baseline and post- treatment (12 months)4
12-month change in failure load at the radius and tibia
Using repeated measures analysis, the investigators will compare change in failure load at the radius and tibia after 12 months of treatment between the transdermal 17β-E2 group and each of the oral 17β-E2 and transdermal EE+LNG groups. Failure load is assessed using microfinite element analysis (N).
Time frame
Baseline and post- treatment (12 months)Secondary outcomes
1
12-month change in IGF-1
Using repeated measures analysis, the investigators will compare change in IGF-1 concentrations after 12 months of treatment between the transdermal 17β-E2 group and the oral 17β-E2 group.
Time frame
Baseline and post-treatment (12 months)2
12-month change in SHBG
Using repeated measures analysis, the investigators will compare change in SHBG concentrations after 12 months of treatment between the transdermal 17β-E2 group and the transdermal EE+LNG group
Time frame
Baseline and post-treatment (12 months)3
Associations of 12-month change in IGF-1 with changes in P1NP
The investigators will use rank correlation analysis for this assessment.
Time frame
12 months4
Associations of 12-month change in SHBG with changes in P1NP
The investigators will use rank correlation analysis for this assessment.
Time frame
12 monthsSponsors and contacts
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University of Virginia
Lead sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
Source ClinicalTrials.gov