Clinical trial NCT03928288: Cabergoline for the Treatment of Chronic Pain Due to Endometriosis
Official title: Novel, Non-Hormonal Therapy for the Treatment of Chronic Pain Due to Endometriosis in Adolescent and Adult Women
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Endometriosis
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Thomas Jefferson University
name: Stanford University
name: Children's Hospital Colorado
name: Brigham and Women's Hospital
First posted: 2019-04-26
Enrollment: 140
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Endometriosis is dependent on angiogenesis (the sprouting of new blood vessels) for its growth and maintenance, but the side effects of currently approved angiogenesis inhibitors make these agents inappropriate for use in reproductive-age patients. This obstacle will be overcome by performing a randomized, double blind clinical trial aimed at repurposing an existing drug, cabergoline, as a safe, alternative angiogenesis inhibitor for adolescents and young women with endometriosis. This trial proposes a novel, non-hormonal, non-surgical therapeutic approach aimed at alleviating the pain and suffering associated with this common chronic disease that currently has limited treatment options.

Detailed description: Endometriosis is a gynecologic condition in which tissue similar to the inside lining of the uterus (the endometrium) grows in locations in the body outside of the uterus. This abnormal growth can cause severe pain, often coinciding with a woman's menstrual period. Endometriosis affects about 10% of all women of reproductive age in the US, and leads to an estimated $22 billion/year in health care costs in the US alone. Endometriosis is a chronic disease that can progress over time, leading to infertility, debilitating pelvic pain, and resulting poor quality of life. Disease management involves not only prompt initiation of therapy, but also the maintenance of therapy for a prolonged length of time. As no cure currently exists, the disease typically progresses until menopause. Current medical management typically consists of hormonal medications and surgery, but these therapies are limited by lack of successful relief of symptoms, cost, or side effects. Many patients have endometriosis pain that is refractory to all available treatments. Safe, well-tolerated, long-duration additions to currently available treatments are sorely needed to ameliorate the chronic course of this disease.

Angiogenesis refers to the generation of new blood vessels from existing vessels. It is required for the growth of new living tissue and has been implicated in the initiation, maintenance, and spread of endometriosis. The investigators hypothesize that medications that inhibit the process of angiogenesis can be used to treat endometriosis. The angiogenesis inhibitor medications that are currently available cause severe side effects such as birth defects that prevent them from being safely used for treating endometriosis in young, otherwise healthy women. In contrast, there is an alternative medication, cabergoline, which has been extensively used in clinical practice for treatment of other endocrine conditions suffered by reproductive-aged women. While cabergoline appears to inhibit angiogenesis, it acts on this process indirectly such that it has very few side effects, making it appropriate for use in young women with endometriosis.

The investigators will conduct a clinical drug trial to determine whether cabergoline is an effective addition to standard hormonal therapy for decreasing persistent pelvic pain suffered by adolescents and young women with surgically-proven endometriosis. Patients who are interested in participating in our study will be randomized (decided by a flip of a coin) to either receive cabergoline, the investigational medication, or a placebo pill (a sugar pill). It is believed that after 6 months, patients who take cabergoline twice a week will demonstrate decreased pain scores and improved quality of life/ability to perform daily activities as compared to patients who take a placebo pill (sugar pill) twice weekly. During the research study, the investigators will study how pain symptoms, menstrual bleeding, levels of inflammation, risk for future cardiac disease, and measures of pain sensitivity change over time by using well-established, validated tools and techniques that the research team has utilized successfully in previous work.

Eligibility criteria: Inclusion Criteria:

* Female with surgically-confirmed endometriosis
* Age 15 years to 40 years
* Current use ≥ 2 months duration of hormonal therapy such as combined oral contraceptives, norethindrone acetate, or levonorgestrel intrauterine device
* Current pelvic pain (score ≥ 3 on Visual Analog Scale, where 0 represents absence of pain and 10 indicates unbearable pain) present for ≥ 14 days/month over the 2 months prior to study enrollment
* Willingness to comply with visit schedule and protocol

Exclusion Criteria:

* Pre-menarche or post-menopause
* Contraindications to cabergoline (e.g., cardiac valve disorder; pulmonary, pericardial, retroperitoneal fibrotic disorder; hypersensitivity to ergot derivatives; uncontrolled hypertension)
* Significant mental or chronic systemic illness that might confound pain assessment or the ability to complete the study
* Pregnant, breastfeeding, or planning to become pregnant in the next 6 months
* Impaired liver function (ALT \> 2x normal) or liver disease
* Breast cancer, current or previous
* Thromboembolic disease, current or previous
* Use of other drugs that affect dopamine (e.g., phenothiazines, metoclopramide, butyrophenones)

Primary outcomes:
measure: Change in pain assessed by the Brief Pain Inventory Interference Scale (BPI) over 6 months
timeFrame: every 6 weeks for 6 months
measure: Change in pain severity measured by Visual Analog Scale (VAS) over 6 months
timeFrame: every 6 weeks for 6 months
measure: Change in pain measured by Biberoglu and Behrman patient ratings scale (B&B pain scale) over 6 months
timeFrame: every 6 weeks for 6 months
Secondary outcomes:
measure: Change in measurements of serum biomarkers of angiogenesis and inflammation over 6 months
timeFrame: every 3 months for 6 months
measure: Change in cardiovascular dysfunction measured by pulse wave velocity over 6 months
timeFrame: baseline and 6 months
measure: Change in measures of central hypersensitization measured by quantitative sensory testing at 6 months
timeFrame: every 3 months for 6 months
measure: Incidence of vaginal bleeding over 6 months
timeFrame: completed daily for 6 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Standford University
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
References: