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Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis (APPOSE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04002141
Recruitment Status : Recruiting
First Posted : June 28, 2019
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
Randomized double blinded placebo-controlled trial to evaluate the impact of ovarian hyperstimulation on endometriosis-related symptoms and to evaluate the impact of letrozole use during ovarian hyperstimulation with respect to endometriosis-related symptoms, embryo/egg quality and quantity, and pregnancy rates.

Condition or disease Intervention/treatment Phase
Endometriosis Ovarian Hyperstimulation Drug: Placebo oral tablet Drug: Letrozole Phase 2

Detailed Description:

Randomized double blinded placebo-controlled trial to evaluate: (1) the impact of letrozole use during ovarian hyperstimulation with respect to endometriosis-related symptoms, embryo/egg quality and quantity, and pregnancy rates, (2) the impact of ovarian hyperstimulation on endometriosis-related symptoms.

There will be a total of 60 participants, 20 participants with endometriosis randomized to the placebo group, 20 participants with endometriosis randomized to the letrozole group and 20 control patients with no history of endometriosis. Letrozole and placebo medication will be started on the first day of gonadotropin injections and continued until the day of trigger shot. Medication will be restarted the night of egg retrieval and continued for 2 weeks post retrieval. Endometriosis associated symptoms will be evaluated using a survey modeled after the clinical survey developed by the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project. Surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Official Title: Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis
Actual Study Start Date : September 17, 2019
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endometriosis
Drug Information available for: Letrozole

Arm Intervention/treatment
Experimental: Endometriosis Letrozole
Participants will be asked to take 5mg letrozole daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to letrozole. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.
Drug: Letrozole
5mg oral daily

Placebo Comparator: Endometriosis Placebo
Participants will be asked to take one tablet placebo daily throughout their ovarian stimulation and for 2 weeks following retrieval. Participants will be blinded to their randomization to placebo. Participants will be asked to complete surveys during their stimulation and up to 12 weeks following retrieval to evaluate endometriosis associated symptoms. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.
Drug: Placebo oral tablet
1 tablet oral daily

No Intervention: No Endometriosis Control
Participants will be asked to complete surveys during their ovarian stimulation and up to 12 weeks following retrieval to evaluate symptoms of pelvic pain. Specifically, surveys will be administered at baseline ultrasound appointment for controlled ovarian hyperstimulation cycle, the day of trigger shot, 3 weeks following egg retrieval, 6 weeks following egg retrieval and 12 weeks following egg retrieval. There will be a total of 20 participants in this arm.



Primary Outcome Measures :
  1. Average Delta in Endometriosis Pain Score Pre and Post Stimulation With and Without Use Of Letrozole [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). ]
    To evaluate how letrozole impacts pain scores throughout controlled ovarian hyperstimulation in patients with endometriosis. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The average delta between pre-stimulation pain score and day of trigger shot pain score will be compared between patients with endometriosis receiving placebo and with endometriosis receiving letrozole.


Secondary Outcome Measures :
  1. Average Delta in Endometriosis Pain Score Pre and Post Stimulation Compared to No Endometriosis [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot). ]
    To evaluate the impact of endometriosis on pain scores throughout controlled ovarian hyperstimulation. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The average delta between pre-stimulation pain score and day of trigger shot will be compared between patients with endometriosis receiving placebo and patients without endometriosis.

  2. Trend in Endometriosis Pain Score Pre and Post Stimulation With Use Of Letrozole [ Time Frame: Pre-stimulation through 12 weeks post retrieval ]
    To evaluate the impact of letrozole on endometriosis pain scores throughout controlled ovarian hyperstimulation. Pain scores will be evaluated using a 0-10 visual acuity scale, where 0 is no pain and 10 is the worst imaginable pain. The trend in pain scores from pre-stimulation through 12 weeks post retrieval will be compared between patients with endometriosis receiving placebo, patients with endometriosis receiving letrozole and patients without endometriosis.

  3. Does Letrozole Impact Embryo and Egg Quantity in Endometriosis [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). ]
    To describe the impact of letrozole on egg/embryo quality in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation. The number of eggs retrieved per AFC and the number of eggs retrieved per total number of mature follicles will be compared between the two groups.

  4. Follicular Fluid [ Time Frame: Baseline ultrasound (day 2 of menstrual cycle) and day 14 (average day of egg retrieval). ]
    To compare follicular fluid average estradiol levels between placebo, letrozole and control groups.

  5. Pregnancy Outcomes [ Time Frame: Up to 2 years. ]
    To compare pregnancy rates in the placebo, letrozole and control groups. Pregnancy will be defined as positive serum hCG after transfer of embryo. The rate will determined by positive hCG per transfer.

  6. Egg Maturity [ Time Frame: Baseline ultrasound to time of cryopreservation of eggs/embryos, which occurs within 7 days of retrieval.. ]
    To describe the impact of letrozole on egg maturity. Measured by number of MII eggs per total number eggs retrieved in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation.

  7. Embryo Grade [ Time Frame: 2 weeks ]
    To describe the impact of letrozole on embryo quality. Measured by fraction of freezable quality embryos (6c or greater, grades 1-2 for symmetry and fragmentation) in patients with endometriosis receiving letrozole and those with endometriosis not receiving letrozole during controlled ovarian stimulation.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18-42 years
  • Planning to undergo controlled ovarian hyperstimulation
  • Prior diagnosis of endometriosis by one of the following: (1) surgical diagnosis (2) endometrioma on pelvic ultrasound
  • Planning to freeze all retrieved oocytes/embryos prior to transfer

Exclusion Criteria:

  • Hypersensitivity to letrozole
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04002141


Contacts
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Contact: Kaitlyn A Wald, MD 415-353-7475 Kaitlyn.Wald@ucsf.edu
Contact: Marcelle I Cedars, MD 415-353-7475

Locations
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United States, California
UCSF Center for Reproductive Health Recruiting
San Francisco, California, United States, 94158
Contact: Kaitlyn Wald, MD    415-353-7475    Kaitlyn.Wald@ucsf.edu   
Contact: Marcelle I Cedars, MD    415-353-7475      
Sponsors and Collaborators
University of California, San Francisco
Investigators
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Principal Investigator: Marcelle I Cedars University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04002141    
Other Study ID Numbers: 18-26544
First Posted: June 28, 2019    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes
Keywords provided by University of California, San Francisco:
Endometriosis
Letrozole
Additional relevant MeSH terms:
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Endometriosis
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs