Cabergoline for Endometriosis

Not currently recruiting at 5 trial locations

Overseen By Esther Kim

Age: < 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Boston Children's Hospital

Must be taking: Hormonal therapy

Must not be taking: Dopamine drugs

Disqualifiers: Pregnancy, Liver disease, Breast cancer, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether cabergoline, a medication already used for other conditions, can treat endometriosis by stopping the growth of new blood vessels that feed the disease. The aim is to find a safer, non-hormonal, and non-surgical treatment option for young women and teens suffering from this painful condition. Participants will receive either cabergoline or a placebo (a pill with no active medicine) to compare results. Women who have had endometriosis confirmed by surgery, experience regular pelvic pain, and have been on hormonal therapy for at least two months might be a good fit for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to potential advancements in endometriosis care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to have been using hormonal therapy for at least 2 months. It also excludes those using drugs that affect dopamine.

Is there any evidence suggesting that cabergoline is likely to be safe for humans?

Research has shown that cabergoline has been tested in over 900 patients for conditions mainly related to hormone levels. Most side effects in these studies were mild or moderate, indicating that patients generally tolerated the treatment well.

Cabergoline also helps reduce blood vessel growth, which is important in treating endometriosis. It achieves this with fewer side effects, making it a promising option for young women with this condition.

Although cabergoline is already approved for other health issues, this trial aims to determine its safety and effectiveness for endometriosis. Since the FDA has approved it for other uses, it might be safe for this new purpose, but this trial will provide more specific information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometriosis?

Unlike the standard treatments for endometriosis, which often include hormonal therapies and pain management medications, cabergoline works by targeting dopamine receptors to reduce prolactin levels. This is exciting for researchers because lowering prolactin might help shrink endometrial tissue and alleviate symptoms without the side effects of traditional hormone therapies. Cabergoline is also taken orally just twice a week, offering a potentially more convenient option for patients compared to daily medications.

What evidence suggests that cabergoline might be an effective treatment for endometriosis?

Research has shown that cabergoline, which participants in this trial may receive, may help treat endometriosis. Studies have found that it can reduce pain and improve quality of life for those with this condition. In tests, cabergoline successfully lowered the activity of endometriosis lesions. This drug works by stopping the growth of new blood vessels, which endometriosis needs to grow. Early results suggest that cabergoline could be a promising non-hormonal option for easing pain in teenagers and young women with endometriosis. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for females aged 15-40 with surgically confirmed endometriosis and chronic pelvic pain. Participants must have been on hormonal therapy for at least 2 months and be willing to follow the study's schedule. It excludes those who are pre-menarche, post-menopause, pregnant, or planning pregnancy soon; have certain heart, lung, liver conditions; breast cancer history; blood clots; or use specific dopamine-affecting drugs.

Inclusion Criteria

I am between 15 and 40 years old.

Willingness to comply with visit schedule and protocol

I have had pelvic pain rated 3 or higher for most days in the last 2 months.

Exclusion Criteria

I am not taking medications that affect dopamine.

I have not started menstruating or I am post-menopausal.

I don't have heart valve issues, fibrosis, allergies to certain migraine medications, or uncontrolled high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cabergoline or placebo twice weekly for 6 months to assess changes in pain and quality of life

6 months

Every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cabergoline

Trial Overview The trial tests Cabergoline as a potential non-hormonal treatment for endometriosis-related pain by inhibiting new blood vessel growth that supports the condition. It's a randomized double-blind study comparing Cabergoline against a placebo to evaluate its effectiveness in reducing pelvic pain.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Cabergoline 0.5 mg PO twice weekly for 6 months

Group II: Placebo Placebo Group 1 Intervention

Placebo capsule PO twice weekly for 6 months

Cabergoline is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Dostinex for:

• Hyperprolactinemia
• Parkinsonian Syndrome

Approved in United States as Dostinex for:

• Hyperprolactinemia
• Parkinsonian Syndrome

Approved in Canada as Dostinex for:

• Hyperprolactinemia
• Parkinsonian Syndrome

Approved in Japan as Dostinex for:

• Hyperprolactinemia
• Parkinsonian Syndrome

Approved in Switzerland as Dostinex for:

• Hyperprolactinemia
• Parkinsonian Syndrome

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Children's Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Thomas Jefferson University

Collaborator

Trials

475

Recruited

189,000+

Published Research Related to This Trial

Cabergoline is more effective than bromocriptine in restarting ovulatory cycles in women with hyperprolactinaemia, based on two comparative trials.

Cabergoline has a lower incidence of nausea compared to bromocriptine and is more convenient to use, requiring only once or twice weekly dosing compared to bromocriptine's multiple daily doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabergoline and hyperprolactinaemia: new preparation. Better than bromocriptine. [2013]

In a study of 120 women with hyperprolactinaemic amenorrhoea, cabergoline was found to be significantly more effective than bromocriptine, achieving normal prolactin levels in 93.3% of patients compared to 48.2% for bromocriptine.

Cabergoline also resulted in fewer gastrointestinal side effects (36.6% vs. 84.5% for bromocriptine), making it a better-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hyperprolactinemic amenorrhea:treatment with cabergoline versus bromocriptine. Results of a national multicenter randomized double-blind study]. Pascal-Vigneron, V., Weryha, G., Bosc, M., et al.[2022]

Cabergoline, a potent prolactin inhibitor used to treat hyperprolactinemia, is being explored for various central nervous system disorders, highlighting its potential therapeutic versatility.

An improved manufacturing process for Cabergoline has been developed that eliminates hazardous reactions, making the production safer and more efficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical synthesis of cabergoline. Ashford, SW., Henegar, KE., Anderson, AM., et al.[2019]

In a pilot study involving 9 women with endometriosis, cabergoline demonstrated a significant reduction in pelvic pain compared to the standard treatment, norethindrone acetate (NETA), suggesting it may be a more effective option for managing endometriosis-associated pain.

Cabergoline was well tolerated with no serious adverse events reported, and it effectively lowered serum levels of vascular endothelial growth factor receptor 1, indicating its potential as a safe and effective nonhormonal treatment targeting the angiogenesis involved in endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate. DiVasta, AD., Stamoulis, C., Gallagher, JS., et al.[2022]

In a pilot study involving 21 adult rats with an endometriosis model, treatment with cabergoline and micronized progesterone for 4 weeks did not lead to significant differences in the size of endometriotic implants compared to a control group.

Although both treatments reduced implant sizes, the lack of statistical significance suggests that longer treatment durations or alternative administration methods should be explored in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Micronized Progesterone and Cabergoline On a Rat Autotransplantation Endometriosis Model: A Placebo Controlled Randomized Trial. Karslıoglu, T., Karasu, AFG., Yildiz, P.[2022]

Cabergoline (CAB) significantly enhances sexual behaviors, including anticipatory motivation and ejaculation, in male rats, indicating its potential efficacy for treating sexual arousal disorders.

Both CAB and its derivative dimethylcabergoline (DMC) show promise in facilitating sexual function with minimal side effects at low doses, suggesting they could be safe treatment options for ejaculation and orgasm disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cabergoline and dimethylcabergoline on the sexual behavior of male rats. Pfaus, JG., Antonie, RA., Dosa, PI., et al.[2023]

Cabergoline is a well-tolerated and effective treatment for hyperprolactinaemia in patients who cannot tolerate or are resistant to bromocriptine, as shown in a study of 10 patients with prolactinoma.

In the study, cabergoline led to successful outcomes such as pregnancy and normalization of prolactin levels in several patients, with significant tumor shrinkage observed in one case, highlighting its potential as a preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the dopamine agonist cabergoline in patients with prolactinoma intolerant or resistant to bromocriptine. Delgrange, E., Maiter, D., Donckier, J.[2019]

Cabergoline (CAB) is a highly effective treatment for hyperprolactinaemia, showing greater potency and longer-lasting effects compared to bromocriptine, with significant tumor shrinkage observed in patients with macroprolactinoma.

CAB is well-tolerated by most patients and is recommended as the first-line treatment for hyperprolactinaemic disorders, although women planning to conceive should discontinue use one month prior to trying to become pregnant due to limited data on its effects during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabergoline. Colao, A., Lombardi, G., Annunziato, L.[2022]

In a study involving 12 women with hyperprolactinemia, cabergoline was found to be more effective than quinagolide in lowering prolactin (PRL) levels, with average levels of 10.7 micrograms/L compared to 25.0 micrograms/L for quinagolide (p < 0.05).

Cabergoline also resulted in a significantly longer time before the recurrence of hyperprolactinemia (14 weeks) compared to quinagolide (5 weeks), indicating its potential for better long-term management of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cross-over study with the two novel dopaminergic drugs cabergoline and quinagolide in hyperprolactinemic patients. Giusti, M., Porcella, E., Carraro, A., et al.[2018]

Both cabergoline (Cb2) and quinagolide effectively inhibit angiogenesis and reduce the size of endometriotic lesions in a mouse model, suggesting their potential as treatments for endometriosis.

Quinagolide, a non-ergot-derived dopamine agonist, shows similar efficacy to Cb2 without the associated risk of cardiac valve regurgitation, making it a safer alternative for future human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis. Delgado-Rosas, F., Gómez, R., Ferrero, H., et al.[2019]

Cabergoline (CAB) effectively normalized prolactin (PRL) levels in 30 female patients with hyperprolactinemia, with significant reductions observed as early as one week into treatment, and many patients maintained normal levels for weeks after stopping the medication.

CAB was generally well tolerated, with fewer patients discontinuing treatment due to side effects compared to bromocriptine, highlighting its potential as a safer long-term option for managing hyperprolactinemic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of long term treatment with cabergoline, a new long-lasting ergoline derivative, in hyperprolactinemic patients. Ciccarelli, E., Giusti, M., Miola, C., et al.[2018]

In a mouse model of endometriosis, both Dienogest (a progestin) and Cabergoline (a dopamine agonist) showed significant therapeutic effects by reducing inflammation in the uterus, peritoneum, and intestine after 14 days of treatment.

The combination of Dienogest and Cabergoline produced a synergistic effect, making it a promising alternative treatment for endometriosis in patients undergoing assisted reproductive technology (ART), where traditional medications are not safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Medicine for Endometriosis and Its Therapeutic Effect in a Mouse Model. Kim, YS., Kim, YJ., Kim, MJ., et al.[2020]

In a study of 119 patients undergoing cabergoline therapy for hyperprolactinemia and acromegaly, the prevalence of clinically relevant valvular regurgitation was similar to that of matched controls, suggesting no significant increase in cardiac valvular fibrosis risk associated with cabergoline use.

The study found that lung function impairment was observed in some patients, but this was not linked to the cumulative dose of cabergoline, indicating that long-term use of the drug may not significantly increase the risk of fibrotic adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of major fibrotic adverse events in hyperprolactinemic patients treated with cabergoline. Lafeber, M., Stades, AM., Valk, GD., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8655411/

Nonhormonal therapy for endometriosis: a randomized ... We observed a decrease in pain scores and increase in pain relief in women randomized to receive cabergoline, who appeared to show similar or more improvements ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03928288

Cabergoline for the Treatment of Chronic Pain Due to ... 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 ...

3. karger.com karger.com/goi/article/doi/10.1159/000546198/926764/Cabergoline-s-Promise-in-Endometriosis-Restoring

Cabergoline's Promise in Endometriosis: Restoring ... In the experimental endometriosis model, both 0.05 mg/kg/day and 0.1 mg/kg/day doses of cabergoline effectively reduced lesion activity, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34934987/

Nonhormonal therapy for endometriosis: a randomized, ... This pilot study suggests that cabergoline, a vascular endothelial growth factor pathway inhibitor, is an effective therapeutic option for women with chronic ...

5. childrenscolorado.org childrenscolorado.org/advances-answers/recent-articles/researching-cabergoline-nonhormonal-endometriosis-treatment/

Nonhormonal Endometriosis Treatment Trial A new clinical trial tests the efficacy of cabergoline, a nonhormonal endometriosis treatment to help reduce pain in adolescents with the ...

6. labeling.pfizer.com labeling.pfizer.com/ShowLabeling.aspx?id=13930

Dostinex Tablets (Cabergoline) 5.3 Preclinical safety data. There were maternotoxic effects but no teratogenic effects in mice given cabergoline at doses up to 8 mg/kg/day (approximately ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf

Dostinex (cabergoline) tablets label - accessdata.fda.gov The safety of DOSTINEX Tablets has been evaluated in more than 900 patients with hyperprolactinemic disorders. Most adverse events were mild or moderate in ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/cabergoline-oral-route/description/drg-20062485

Cabergoline (oral route) - Side effects & dosage Safety and efficacy have not been established. Geriatric. Appropriate studies performed to date have not demonstrated geriatric-specific ...

9. my.clevelandclinic.org my.clevelandclinic.org/health/drugs/20863-cabergoline-tablets

Cabergoline (Dostinex): Uses & Side Effects Cabergoline (Dostinex) treats high levels of prolactin. Prolactin is a hormone that's responsible for lactation and certain breast tissue development.