Transdermal Estrogen in Women With Anorexia Nervosa

• ClinicalTrials.gov Identifier: NCT03875378
• Recruitment Status: Recruiting
• First Posted: March 14, 2019
• Last Update Posted: May 9, 2022
• Sponsor: Pouneh K. Fazeli, MD
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Pouneh K. Fazeli, MD, University of Pittsburgh

Study Description

Brief Summary:

Randomized, placebo-controlled study investigating the use of physiologic, transdermal estrogen for low bone mass in adult women with anorexia nervosa.

Condition or disease	Intervention/treatment	Phase
Anorexia Nervosa	Drug: Transdermal estrogen; Drug: Placebos	Phase 2

Detailed Description:

Anorexia nervosa is a prevalent psychiatric with a lifetime prevalence of up to 2.2%. Among the many medical co-morbidities associated with anorexia nervosa, the most common is significant bone loss, which can persist despite weight recovery. Nearly 90% of women with anorexia nervosa have osteopenia and this low bone mass is associated with an increased fracture risk. Nearly 30% of women with anorexia nervosa report a history of a fracture and a prospective study demonstrated a 7-fold increased risk of fracture in women with anorexia nervosa compared to age-matched controls. Because anorexia nervosa is a chronic disease that can persist despite psychiatric and nutritional counseling, the bone loss and increased fracture risk can persist and lead to lifelong morbidity. Therefore, finding a treatment for bone loss associated with anorexia nervosa is of critical importance.

This 18-month randomized, placebo-controlled study will investigate in women (ages 20 to 45 years old) with anorexia nervosa whether treatment with transdermal estrogen replacement will increase bone mineral density (BMD).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Transdermal Estrogen for the Treatment of Bone Loss in Women With Anorexia Nervosa
• Actual Study Start Date: August 28, 2020
• Estimated Primary Completion Date: August 30, 2023
• Estimated Study Completion Date: August 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Transdermal estrogen/progesterone; Transdermal estradiol (0.045mg)/levonorgestrel (0.015mg) patch applied weekly for 18 months	Drug: Transdermal estrogen; Transdermal estradiol (0.045mg)/levonorgestrel (0.015mg) weekly patch
Placebo Comparator: Placebo; Placebo patch applied weekly for 18 months	Drug: Placebos; Placebo weekly patch

Outcome Measures

Primary Outcome Measures :

1. Change in bone mineral density at 18 months [ Time Frame: Baseline, 18 months ]
   Change in lumbar spine bone mineral density at 18 months

Secondary Outcome Measures :

1. Change in bone mineral density at hip at 18 months [ Time Frame: Baseline, 18 months ]
   Change in total hip bone mineral density at 18 months
2. Change in bone mineral density at femoral neck at 18 months [ Time Frame: Baseline, 18 months ]
   Change in femoral neck bone mineral density at 18 months
3. Change in parameters of bone microarchitecture at 18 months [ Time Frame: Baseline, 18 months ]
   Change in microarchitectural parameters as measured by high-resolution peripheral quantitative CT at 18 months
4. Change in estimated bone strength at 18 months [ Time Frame: Baseline, 18 months ]
   Change in estimated bone strength as assessed by finite element analysis at 18 months
5. Change in vertebral fractures at 18 months [ Time Frame: Baseline, 18 months ]
   Change in vertebral fractures as assessed by vertebral fracture assessment at 18 months

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Female
2. 19-45 years of age
3. DSM-5 psychiatric criteria for anorexia nervosa
4. <85% of ideal body weight as defined by the 1983 Metropolitan Life Insurance Height and Weight Tables
5. Amenorrhea
6. T-score of < -1.0 at spine or hip

Exclusion Criteria:

1. Diseases known to affect bone metabolism, including untreated thyroid dysfunction, vitamin D deficiency, Cushing's syndrome, diabetes mellitus or renal insufficiency (eGFR < 60)
2. Personal history of venous or arterial clot
3. History of stroke or myocardial infarction
4. History of hypercoagulable disorder
5. Personal history or history of a first-degree relative with breast cancer
6. History of hereditary angioedema
7. Any medication known to affect bone metabolism, including systemic glucocorticoids within three months of the baseline visit, depot medroxyprogesterone within 6 months of the baseline visit, oral bisphosphonates within one year of the baseline visit or IV bisphosphonates within three years of the baseline visit
8. Bone fracture within the prior 12 months
9. Serum potassium < 3.0 meq/L, serum ALT > 3 times the upper limit of normal or Hemoglobin < 10 g/dL
10. Fasting serum triglyceride level > 150 mg/dL
11. Pregnant or breastfeeding (or desiring pregnancy within the next 18 months)
12. Active substance abuse
13. Elevated PTH level
14. 25-OH vitamin D level < 20 ng/mL
15. Low phosphorus level

Contacts and Locations

Contacts

Contact: Pouneh Fazeli, MD; 412-648-9761; pkfazeli@pitt.edu

Contact: Shari Reynolds; 412-383-0570

Locations

United States, Pennsylvania

University of Pittsburgh School of Medicine; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contact: Pouneh K Fazeli, MD 412-648-9761 pkfazeli@pitt.edu

Contact: Shari Reynolds 412-383-0570

Sponsors and Collaborators

Pouneh K. Fazeli, MD

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Pouneh Fazeli, MD; University of Pittsburgh

More Information

• Responsible Party: Pouneh K. Fazeli, MD, Associate Professor of Medicine, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT03875378
• Other Study ID Numbers: STUDY19070395; R01HD099139 ( U.S. NIH Grant/Contract )
• First Posted: March 14, 2019
• Last Update Posted: May 9, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The final dataset will include self-reported demographic and behavioral data from interviews with the subjects, laboratory data from blood specimens provided and radiologic images of subjects with anorexia nervosa. Because anorexia nervosa is a psychiatric disease and we will be collecting identifying information, even though the final dataset will be stripped of identifiers prior to release for sharing, we believe that the information disclosed by the subjects should be protected in the most stringent way possible in order to prevent possible identification of subjects. Thus, we will make the data and associated documentation available to users only under a data-sharing agreement that provides for: 1) a commitment to using the data only for research purposes and not to identify any individual participant; 2) a commitment to securing the data using appropriate computer technology; and 3) a commitment to destroying or returning the data after analyses are completed.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: 12 months after publication and no pre-specified end date.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Pouneh K. Fazeli, MD, University of Pittsburgh:

Bone mineral density; Estrogen

Additional relevant MeSH terms:

Anorexia; Anorexia Nervosa; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Mental Disorders; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs