Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pilot Study of the IL-1 Antagonist Anakinra for the Treatment of Endometriosis Related Symptoms

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: NCT03991520
Recruitment Status : Not yet recruiting
First Posted : June 19, 2019
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
Sanjay Agarwal, University of California, San Diego

Brief Summary:
All current FDA approved medications to treat endometriosis pain including danazol, GnRH agonists (Lupron, Zoladex and Synarel), GnRH antagonist (elagolix) and depo-provera prevent or contradict pregnancy. Therefore women suffering from endometriosis and trying to conceive have no medical options apart from pain meds. The purpose of this pilot study is to determine whether the anti-inflammatory, IL-1 inhibitor (anakinra) reduces pelvic pain due to endometriosis without altering menstrual cycles, which is an indicator of ovulatory function. Anakinra is an FDA approved injectable medication for the treatment of rheumatoid arthritis that is pregnancy category B.

Condition or disease Intervention/treatment Phase
Endometriosis Anakinra Markers of Inflammation Drug: Anakinra 100Mg/0.67Ml Inj Syringe Drug: Placebo Early Phase 1

Detailed Description:

Endometriosis is a chronic inflammatory disease1 that affects 5 -10% of reproductive aged women1,2. It is characterized by the presence of uterine endometrium outside the uterus. The condition causes health distress through pelvic pain and decreased QOL. Current therapies to temporarily control symptoms include surgery as well as medical options that prevent pregnancy and have significant side-effects.3,4 The most common symptoms with endometriosis include dysmenorrhea, dyspareunia and NMPP. Ultimately these lead to a decrease in QOL. All current medical therapies to treat endometriosis pain prevent or contradict pregnancy.

Inflammation is a well-established central figure in the pathophysiology of endometriosis(1). Increasingly, data is suggesting that IL-1 is a mediator of inflammation in endometriosis (2, 3). In addition, there are data that single nucleotide polymorphisms at the IL-1A gene locus are associated with endometriosis risk (4). Hence, it is rational to assess anakinra, an IL-1 antagonist, in the control of symptoms and inflammation due to endometriosis. Therefore, we propose this pilot study testing an FDA approved medication (anakinra) to reduce IL-1 and on dysmenorrhea due to endometriosis without stopping periods (a sign of ovulation).

Anakinra is a self-administered subcutaneous injectable medication that is FDA approved for the treatment of rheumatoid arthritis. As an IL-1 antagonist, it works by decreasing inflammation and is administered daily by the patient. Because Anakinra interferes with the immune system functioning, the major concern with the use of Anakinra is reduced resistance to infection. Others include injection site reactions such as redness, itching, rash, and pain. Bruising or bleeding also can occur, but it is rare. These effects usually stop after one - two weeks. Headaches and low white blood cell counts can also occur, but these are very rare. Anakinra should be used with caution in those with chronic kidney disease.

Anakinra is not specifically FDA approved for endometriosis. Although no data on its use in women with endometriosis have been published, there is no reason to expect women with endometriosis would be at any particular or increased risk than those in the general population.

This study is a randomized, double blinded, placebo controlled, cross-over clinical pilot study of 20 women. Patients diagnosed with laparoscopically proven endometriosis within the last 5 years will be randomized to either treatment with an FDA approved medication (Anakinra) or a placebo. This is an investigator initiated single center study sponsored by the Swedish Orphan Biovitrum (SOBI). SOBI will provide the study drug and placebo.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Pilot Study of the IL-1 Antagonist Anakinra for the Treatment of Endometriosis Related Symptoms
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endometriosis
Drug Information available for: Anakinra

Arm Intervention/treatment
Experimental: Active Treatment with Anakinra
10 subjects will be enrolled in this group. Initial treatment will consist of 100mg/day Anakinra, which is the standard, FDA approved dose for the treatment of rheumatoid arthritis. The randomized treatment will be self-administered by the subject each evening by subcutaneous injection from within 24 hours of the onset of menses until within 24 hours of last menstrual day.
Drug: Anakinra 100Mg/0.67Ml Inj Syringe
The study drug is100mg/day Anakinra, which is the standard, FDA approved dose for the treatment of rheumatoid arthritis. The randomized treatment will be self-administered by the subject each evening by subcutaneous injection.
Other Name: Kineret

Placebo Comparator: Standard Comparison
10 subjects will be enrolled in this group. This group will be given placebo injections as their initial treatment. The placebo is comparable to the anakinra formulation without the active medication - a solution (pH 6.5) containing anhydrous citric acid (1.29 mg), disodium EDTA (0.12 mg), polysorbate 80 (0.70 mg), and sodium chloride (5.48 mg) in water for injection. These individuals will self-administer the placebo each evening by subcutaneous injection from within 24 hours of the onset of menses until within 24 hours of last menstrual day.
Drug: Placebo
The placebo is comparable to the anakinra formulation without the active medication - a solution (pH 6.5) containing anhydrous citric acid (1.29 mg), disodium EDTA (0.12 mg), polysorbate 80 (0.70 mg), and sodium chloride (5.48 mg) in water for injection




Primary Outcome Measures :
  1. Comparison of the impact of anakinra versus placebo on menstrual pain (dysmenorrhea) using the modified Biberoglu and Behrman scale. [ Time Frame: Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods. ]
    The primary pain outcome measure is to determine the impact of anakinra on dysmenorrhea due to endometriosis, using the modified Biberoglu and Behrman scale. The modified Biberoglu and Behrman scale consists of three patient-reported symptoms (dysmenorrhea, dyspareunia, and non-menstrual pelvic pain). Each of these is separately graded on a scale from 0 to 3, with a max of 9 and higher numbers indicating more severe symptoms. Changes in dysmenorrhea is the primary endpoint.


Secondary Outcome Measures :
  1. Comparison of the impact of anakinra versus placebo on dyspareunia and non menstrual pelvic pain using the modified Biberoglu and Behrman scale. [ Time Frame: Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods. ]
    Secondary pain outcome measures are to determine the impact of anakinra on dyspareunia and non-menstrual pelvic pain due to endometriosis, using the modified Biberoglu and Behrman scale. The modified Biberoglu and Behrman scale consists of three patient-reported symptoms (dysmenorrhea, dyspareunia, and non-menstrual pelvic pain). Each of these is separately graded on a scale from 0 to 3, with a max of 9 and higher numbers indicating more severe symptoms. Changes in dyspareunia and non-menstrual pelvic pain are secondary pain endpoints.

  2. Comparison of the impact of anakinra versus placebo on the quality of life using the Endometriosis Health Profile 30 questionnaire (EHP-30), conducted after each course of study medication administration. [ Time Frame: Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods. ]
    The secondary outcome measure is to determine the impact of anakinra on the quality of life due to endometriosis, using the Endometriosis Health Profile 30 (EHP-30) questionnaire. The EHP-30 consists of a 30 item instrument that assesses pain, control and powerlessness, social support, emotional well-being, and self image. Each scale is standardized on a scale of 0 - 100, where 0 indicates the best health status through to 100 worst health status.

  3. Comparison of serum inflammatory markers before and after anakinra administration. [ Time Frame: There will be blood tests at the start and end of each of of the subject's next 6 menstrual periods for a total of 12 blood draws. ]
    The secondary outcome is to evaluate the effect of anakinra on serum inflammatory markers that are elevated in women with endometriosis. Relevant inflammatory markers of endometriosis include CRP, CA125, IL-1, IL-4, IL-6, IL-10, BDNF, Glycodelin, and ZAG. There will be blood tests at the start and end of each of of the subject's next 6 menstrual periods: At the time of each blood draw, we will collect 20 mL (approximately 4 teaspoons) of blood. This will be needed for each of the 6 study menstrual periods for a total of 12 blood draws. There will be a total of 240 ml of blood or approximately 16 tablespoons of blood collected throughout the entire study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   The primary aim of this study is to determine the impact of anakinra on menstrual pain due to endometriosis. Therefore, only women will be eligible for this study.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women aged 18-40 with regular menstrual periods every 24-32 days and not lasting more than 6 days per month
  • Laparoscopically proven endometriosis within the last 5 years.
  • At least a moderate level of menstrual pain based on the patient reported parameters of the B&B pain scale (>4/9) with dysmenorrhea being scored at least 2/3.
  • Off hormonal contraceptives for at least 1 month.
  • Off other hormonal therapy including depot provera (DMPA) for endometriosis for at least 3 months.
  • Willingness to use one of the following to prevent pregnancy:
  • Double method: barrier contraception with spermicide
  • IUD in place
  • Sterilization

Exclusion Criteria:

  • History of hysterectomy or oophorectomy.
  • Non-response to GnRH agonist/antagonist, DMPA, aromatase inhibitors or danazol.
  • Currently pregnant or attempting pregnancy.
  • Contraindication to anakinra.
  • Chronic kidney disease stage 4 and 5 or creatinine clearance <30mL/min/1.73m2.
  • Abnormal LFTs, CBC or serum electrolytes including estimated GFR.
  • Patient refusal.
  • Plan to receive a live vaccine

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): NCT03991520


Contacts
Layout table for location contacts
Contact: Vy Tran, MS 8582495419 vyt003@ucsd.edu
Contact: Emily Liu, BS 8587057060 t9liu@ucsd.edu

Locations
Layout table for location information
United States, California
UCSD Reproductive Endocrinology Not yet recruiting
La Jolla, California, United States, 92037
Contact: Vy Tran, MS    858-249-5419    vyt003@ucsd.edu   
Contact: Emily Liu, BS    8587057060    t9liu@ucsd.edu   
Sub-Investigator: Warren Foster, PhD         
Sponsors and Collaborators
University of California, San Diego
Investigators
Layout table for investigator information
Principal Investigator: Sanjay K Agarwal, MD UC San Diego

Publications:
Layout table for additonal information
Responsible Party: Sanjay Agarwal, Professor and Director of Fertility Services, University of California, San Diego
ClinicalTrials.gov Identifier: NCT03991520     History of Changes
Other Study ID Numbers: 182006
First Posted: June 19, 2019    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Only the PI, Dr. Foster and the study staff will have access to study subjects' research data.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Inflammation
Endometriosis
Pathologic Processes
Genital Diseases, Female
Interleukin 1 Receptor Antagonist Protein
Citric Acid
Antirheumatic Agents
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action