Clinical trial NCT03724955: Pilot E2 for Hypogonadal Women With CFBD
Official title: Pilot Study Evaluating the Effects of Estradiol for Hypogonadal Women With Cystic Fibrosis and Osteopenia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Cystic Fibrosis Related Bone Disease
Keywords: Hypogonadism
Estrogen Supplement
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2018-10-30
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, double-blinded, randomized, placebo-controlled, interventional
Primary purpose: TREATMENT

Brief summary: The study is a prospective, double blinded, placebo controlled, randomized study to evaluate the effects of daily oral estrogen supplements on bone health, sexual and reproductive health, quality of life and markers of inflammation and lung function when given to hypogonadal women with Cystic Fibrosis related Bone Disease (CFBD).

Detailed description: Cystic fibrosis (CF) is the most common fatal heritable disease in non-Hispanic whites; CF results in frequent lung infections, chronic inflammation and progressive lung failure. With advancements in medical care, patients with CF are living longer. The median survival of women with CF born and diagnosed in 2010 is projected to be 37 years. Patients with CF are now living long enough to develop comorbidities like Cystic Fibrosis related Bone Disease (CFBD), hypogonadism manifesting as pubertal delay, premature ovarian insufficiency or hypothalamic hypogonadism. These comorbidities in women without CF can be improved by estrogen supplementation.

It is well established that treating hypogonadal (low estrogen levels) women with estrogen can improve their bone health, slow the rate of bone loss and decrease bone turnover markers. Supplemental estrogen given to hypogonadal women can improve sexual and reproductive health including reduction of perimenopausal symptoms and improvement in sexual function which can improve quality of life. There is very little research investigating the effects of estrogen treatment for hypogonadal women with CF. The purpose of this study is to test the hypothesis that daily oral estrogen supplements given to hypogonadal women with CFBD will improve their bone health, sexual and reproductive health, and quality of life and modify markers of inflammation and lung function.

Eligibility criteria: Inclusion Criteria:

* Adult and adolescent female CF patients (age ≥ 18 years),
* presenting to the CF clinic for routine follow up of cystic fibrosis,
* hypogonadal women defined as E2 level \< 25,
* dual energy X-ray absorptiometry (DEXA) scan within 2 years of enrollment with T- or Z-score \< -1,
* able to tolerate oral medications.

Exclusion Criteria:

* Inability to obtain or declined informed consent from the subject and/or legally authorized representative,
* Pregnancy,
* Too ill to participate in study based on investigator's or study team's opinion,
* Current use of systemic estrogen,
* History of thromboembolic event within the previous 2 years,
* History of migraines with aura,
* Hypercoagulability including previous diagnosis of Factor V Leiden or Protein C or S deficiency,
* Current smoker,
* History of diagnosis with breast or uterine cancer,
* Current significant liver disease with cholelithiasis or cirrhosis,
* Status post lung or liver transplantation,
* Current use of systemic steroids

Primary outcomes:
measure: Change in serum estradiol level in picograms per milliliter (pg/mL) from baseline to 6 months among the treatment and placebo groups
timeFrame: Baseline/Enrollment visit and at 6 months
Secondary outcomes:
measure: Change in Serum carboxy-terminal collagen crosslinks (CTX-1) from baseline to 6 months among the treatment and placebo groups
timeFrame: Baseline/Enrollment visit and at 6 months
measure: change in of Serum Procollagen I Intact N-Terminal (P1NP) measured in mcg/L from baseline to 6 months among the treatment and placebo groups
timeFrame: Baseline/Enrollment visit and at 6 months
measure: Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory score from baseline to 6 months among the treatment and placebo groups
timeFrame: Baseline/Enrollment visit and at 6 months
measure: Change in percentage of FEV1 from baseline to 6 months among the treatment and placebo groups
timeFrame: Baseline/Enrollment visit and at 6 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Vin Tangpricha, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu M, Tirouvanziam R, Arora N, Tangpricha V. Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease. Pilot Feasibility Stud. 2021 Aug 19;7(1):160. doi: 10.1186/s40814-021-00897-x.