Cabergoline for Endometriosis

Recruiting at 5 trial locations

Overseen By Maddie Smith

Age: < 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing cabergoline, a medication that stops new blood vessels from forming, to see if it can reduce pain in adolescents and young women with endometriosis. Current treatments often don't work well or have too many side effects. Cabergoline may offer a safer, long-term solution by preventing the growth of new blood vessels needed for endometriosis to grow. Cabergoline has shown promise in early studies for treating chronic pain due to endometriosis.

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.

What evidence supports the effectiveness of the drug Cabergoline for treating endometriosis?

Research shows that Cabergoline, a dopamine agonist, can reduce the size of endometriotic lesions and inhibit new blood vessel formation, which is important for the growth of these lesions. In animal studies, Cabergoline was as effective as other treatments in reducing inflammation and lesion size, suggesting it could be a useful option for managing endometriosis. ^{1 2 3 4 5}

Is cabergoline generally safe for human use?

Cabergoline is generally well-tolerated in humans, with common side effects including nausea, low blood pressure, headache, stomach pain, dizziness, and weakness, which often improve over time. However, it is associated with an increased risk of fibrotic adverse reactions (thickening of tissues), such as cardiac valvular fibrosis, pleuropulmonary, and retroperitoneal fibrosis. ^{6 7 8 9 10}

How does the drug cabergoline differ from other treatments for endometriosis?

Cabergoline is unique because it is a dopamine agonist that primarily suppresses prolactin, a hormone, by acting on dopamine receptors, and it is taken only once or twice a week, unlike other treatments that may require more frequent dosing. It is also known for having fewer side effects like nausea compared to similar drugs like bromocriptine. ^{4 7 11 12 13}

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Cabergoline (Dopamine Agonist)

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.

Participant Groups

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 Canada, Japan, Switzerland for the following indications:

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+

Findings from Research

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 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 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 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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Medicine for Endometriosis and Its Therapeutic Effect in a Mouse Model. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

The Effects of Micronized Progesterone and Cabergoline On a Rat Autotransplantation Endometriosis Model: A Placebo Controlled Randomized Trial. [2022]

4. France pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis. [2019]

6. Italy pubmed.ncbi.nlm.nih.gov

A cross-over study with the two novel dopaminergic drugs cabergoline and quinagolide in hyperprolactinemic patients. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Cabergoline. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Absence of major fibrotic adverse events in hyperprolactinemic patients treated with cabergoline. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of long term treatment with cabergoline, a new long-lasting ergoline derivative, in hyperprolactinemic patients. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

A practical synthesis of cabergoline. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

Effects of cabergoline and dimethylcabergoline on the sexual behavior of male rats. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Effects of the dopamine agonist cabergoline in patients with prolactinoma intolerant or resistant to bromocriptine. [2019]

13. France pubmed.ncbi.nlm.nih.gov

[Hyperprolactinemic amenorrhea:treatment with cabergoline versus bromocriptine. Results of a national multicenter randomized double-blind study]. [2022]