Estrogen Supplementation for Cystic Fibrosis

(STURDY Trial)

Overseen By Cynthia Wang

Age: Any Age

Sex: Female

Trial Phase: Phase 4

Sponsor: Johns Hopkins University

Must not be taking: Anti-osteoporosis, Systemic estrogen, Glucocorticoids

Disqualifiers: Pregnancy, Transplant, Clot risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how estrogen and other hormones affect bone development in young women with cystic fibrosis (CF). It consists of two parts: one observes the impact of different birth control methods on bone health, and the other tests estrogen patches (transdermal estrogen) to determine if they improve bone health and quality of life. Females with CF who have experienced at least one menstrual cycle and plan to use the same type of estrogen supplementation during the study may be suitable candidates. Participants in the patch part of the study should show signs of low estrogen. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are using systemic estrogen (like estrogen-containing birth control pills), you cannot participate in the feasibility sub-study. Also, if you are on anti-osteoporosis therapy or chronic systemic glucocorticoids, you cannot join the observational study.

What is the safety track record for these treatments?

Research has shown that transdermal estrogen patches, like those used in this study, are generally easy to use. Some users might experience mild skin irritation at the application site. One study found no major changes in blood tests, indicating good safety. However, some women with a uterus have reported moderate bleeding.

Regarding cyclic progesterone, evidence indicates that hormonal contraceptives, which often contain progesterone, are safe for women with cystic fibrosis (CF). No clear connection exists between these contraceptives and worsening CF symptoms, suggesting that progesterone is also well-tolerated.

Both treatments have been used previously with few serious side effects, suggesting they are likely safe for participants in this study. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using transdermal estrogen for cystic fibrosis because it offers a novel way to address symptoms by potentially improving bone density and hormone balance. Unlike traditional treatments that focus primarily on managing respiratory symptoms and infections, such as antibiotics and airway clearance techniques, this approach targets the hormonal imbalance that can affect bone health in cystic fibrosis patients. The transdermal delivery method, through skin patches, ensures a steady release of estrogen, which might enhance patient compliance compared to oral medications. This innovative angle could improve overall health outcomes for those with cystic fibrosis, offering a complementary strategy alongside existing therapies.

What evidence suggests that transdermal estradiol might be an effective treatment for bone health in cystic fibrosis?

Research has shown that an estrogen skin patch, known as transdermal estradiol, can stabilize hormone levels and protect against bone loss. This has been proven in postmenopausal women and appears promising for young women with cystic fibrosis (CF) as well. Estrogen use is also linked to improved quality of life scores in individuals with CF, suggesting it might enhance daily well-being. In this trial, some participants will receive transdermal estradiol along with cyclic progesterone. However, limited evidence exists on how cyclic progesterone affects bone health in women with CF. Hormonal birth control, which includes progesterone, typically does not worsen CF. These findings suggest that using both the estrogen patch and cyclic progesterone could enhance bone health and overall well-being in women with CF. ^{1 2 3 5 6}

Who Is on the Research Team?

Malinda Wu, MD, MSc

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for young women with cystic fibrosis who have low estrogen levels, are not pregnant, and agree to use non-estrogen contraception. They should be planning to maintain their current level of estrogen supplementation throughout the study and must be at least two years post their first menstrual cycle.

Inclusion Criteria

I meet all the criteria mentioned and am under 35 years old.

It has been over 2 years since my first period.

I have been diagnosed with cystic fibrosis.

Exclusion Criteria

In the opinion of the CF care team or study investigators participant should not participate in the study

Inability to provide informed consent/assent

I am on long-term steroid medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational Study

Participants will complete three study visits (baseline, 6 months, and 12 months) involving DXAs (bone density assessment), x-rays, blood draws, and questionnaires.

12 months

3 visits (in-person)

Feasibility Sub-study

Participants will apply transdermal estradiol patches once weekly for 12 months, fill out brief quality-of-life surveys in between study visits, and complete blood draws and questionnaires at four study visits.

12 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo patch
• Placebo pill
• Progesterone
• Transdermal estrogen

Trial Overview The study examines how hormonal contraception affects bone health in CF patients and tests the feasibility of transdermal estradiol (estrogen skin patches). Participants will undergo blood tests, questionnaires, x-rays, and DXAs over a year to monitor changes in bone health.

How Is the Trial Designed?

Group I: Transdermal Estradiol/Cyclic Progesterone Experimental Treatment 2 Interventions

Participants will apply transdermal estradiol patches (0.1 mg/day) weekly for 12 months following baseline study visits. Participants not already using a progesterone-containing contraceptive will also take progesterone (200 mg) for 10 days per month.

Group II: Observational Study Active Control 1 Intervention

Participants will complete three study visits (baseline, 6 months, and 12 months) involving DXAs (bone density assessment), x-rays, blood draws, and questionnaires.

Transdermal estrogen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Estradiol patch for:

• Menopause symptoms
• Osteoporosis prevention
• Hormone replacement therapy

Approved in European Union as Estradiol patch for:

• Menopause symptoms
• Osteoporosis prevention
• Hormone replacement therapy

Approved in Canada as Estradiol patch for:

• Menopause symptoms
• Osteoporosis prevention
• Hormone replacement therapy

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Cystic Fibrosis Foundation

Collaborator

Trials

199

Recruited

37,800+

Published Research Related to This Trial

The estradiol transdermal therapeutic system effectively delivers estradiol to maintain premenopausal levels in postmenopausal women, helping to protect against osteoporosis and reduce fracture risk with minimal dosages.

This method of delivery is well-tolerated, with local irritation being the most common side effect, and it offers similar benefits for menopausal symptoms as oral estrogens, making it a promising alternative for estrogen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal estradiol. A review of its pharmacological profile, and therapeutic potential in the prevention of postmenopausal osteoporosis. Balfour, JA., McTavish, D.[2018]

The novel 17 beta-Estradiol patch provides stable blood concentrations over 3 to 4 days, avoiding peaks that can occur with existing transdermal products, which may enhance safety and efficacy in hormone therapy.

The patch size directly correlates with the bioavailability of 17 beta-Estradiol, demonstrating a consistent drug delivery rate of approximately 48 micrograms per day, indicating a reliable and optimized method for hormone substitution therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Kinetics of a new patch for transdermal administration of 17 beta-estradiol]. Rohr, UD., Nauert, C., Ehrly, AM.[2013]

The new 7-day estrogen matrix patch (Climara) effectively alleviates climacteric symptoms in postmenopausal women, showing positive results in two 11-week placebo-controlled studies with good tolerance across different doses.

The 7-day patch demonstrated superior adhesion compared to the Estraderm patch, and absorption of estradiol was found to be higher and more consistent when applied to the buttock rather than the abdomen, indicating potential for optimized application sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with a 7-day estrogen patch: principles and practice. Notelovitz, M.[2013]

The seven-day transdermal estradiol patch significantly reduced menopausal symptoms over six months, as indicated by a decrease in the average climacteric score from 27.18 at admission to 12.18 by the end of the study.

The patch demonstrated excellent adhesion with over 94% remaining securely in place, and it was generally well tolerated, with skin irritation being the most common side effect, primarily itching.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and acceptability of a seven-day, transdermal estradiol patch for estrogen replacement therapy. Jarupanich, T., Lamlertkittikul, S., Chandeying, V.[2013]

The new estradiol transdermal patch, applied once weekly, effectively increased plasma estradiol levels in postmenopausal women, achieving average concentrations proportional to the patch strength (25, 50, and 75 micrograms/day) over a 7-day period.

The patches were well tolerated with only mild and transient skin reactions, and they showed good systemic tolerability, making them a practical option for long-term estrogen replacement therapy to manage postmenopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol and estrone plasma levels during application of three strengths of a 7-day estradiol transdermal patch. Setnikar, I., Rovati, LC., Santoro, A., et al.[2013]

The Estraderm Transdermal System, which delivers 17-beta estradiol, is an effective method for estrogen replacement therapy, providing relief from climacteric symptoms similar to oral estrogens, with localized skin irritation as the primary side effect in about 15% of users.

Transdermal estrogen therapy may have advantages over oral estrogen, such as bypassing the liver to reduce risks associated with blood pressure elevation, but there are concerns about an increased risk of breast cancer, highlighting the need for further long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen replacement therapy and the estraderm transdermal system. Youngkin, EQ.[2013]

The estradiol transdermal therapeutic system effectively delivers estradiol to postmenopausal women, maintaining physiological hormone levels while avoiding first-pass metabolism, which is a common issue with oral estrogen therapies.

Clinical studies indicate that transdermal estradiol is comparable in efficacy to oral and subcutaneous estrogens for managing menopausal symptoms and has a favorable safety profile, with local irritation being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal estradiol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of menopausal complaints. Balfour, JA., Heel, RC.[2018]

The new matrix transdermal patch with lauric acid showed improved stability in estradiol delivery compared to traditional matrix and reservoir patches, with more consistent plasma levels in postmenopausal women.

Both the prototype and its industrial counterpart provided similar estradiol absorption, achieving higher plasma concentrations than the reference matrix patch, indicating enhanced bioavailability for hormone replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estradiol pharmacokinetics after transdermal application of patches to postmenopausal women: matrix versus reservoir patches. Reginster, JY., Donazzolo, Y., Brion, N., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7494372/

Contraceptive use among women with cystic fibrosis Both contraceptive use and unplanned pregnancy among women with CF are common. Associations between hormonal contraceptive use and adverse pulmonary or bone ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11025598/

Contraceptive safety among women with cystic fibrosis Overall, there is limited evidence suggesting that hormonal contraceptive use does not negatively impact disease severity among women with CF (body of evidence ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1569199325000062

Contraceptive use and pregnancy in cystic fibrosis This study explores contraceptive use, pregnancy trends, and whether concomitant cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy ...

4. publications.ersnet.org publications.ersnet.org/content/erj/41/1/67

Oral contraceptives do not appear to affect cystic fibrosis ... Here, we conducted a retrospective study aimed at assessing the effect of OC use in females with CF. Our data suggest that OC use does not affect CF disease ...

5. contraceptionjournal.org contraceptionjournal.org/article/S0010-7824(15)00480-1/fulltext

Contraception in women with cystic fibrosis: a systematic ... Overall, the data on efficacy and safety of hormonal contraception in women with CF are quite limited, with a paucity of large, prospective studies. · The most ...

6. stacks.cdc.gov stacks.cdc.gov/pdfjs/web/viewer.html?file=https://stacks.cdc.gov/view/cdc/154553/cdc_154553_DS1.pdf&

Contraceptive safety among women with cystic fibrosis Contraceptive safety among women with cystic fibrosis: a systematic review. Maura K. Whitemana,*, Titilope Oduyeboa, Lauren B. Zapataa, Seth Walkerb, ...