Cabergoline for Endometriosis
Recruiting in Palo Alto (17 mi)
+5 other locations
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.
12345Is 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.
678910How 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.
47111213Eligibility 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.
+2 more
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.
+5 more
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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: InterventionExperimental Treatment1 Intervention
Cabergoline 0.5 mg PO twice weekly for 6 months
Group II: PlaceboPlacebo Group1 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:
πͺπΊ Approved in European Union as Dostinex for:
- Hyperprolactinemia
- Parkinsonian Syndrome
πΊπΈ Approved in United States as Dostinex for:
- Hyperprolactinemia
- Parkinsonian Syndrome
π¨π¦ Approved in Canada as Dostinex for:
- Hyperprolactinemia
- Parkinsonian Syndrome
π―π΅ Approved in Japan as Dostinex for:
- Hyperprolactinemia
- Parkinsonian Syndrome
π¨π Approved in Switzerland as Dostinex for:
- Hyperprolactinemia
- Parkinsonian Syndrome
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Childrens Hospital ColoradoAurora, CO
Standford UniversityPalo Alto, CA
Brigham and Women's HospitalBoston, MA
Beth Israel Deaconess Medical CenterBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
Boston Children's HospitalLead Sponsor
Stanford UniversityCollaborator
Children's Hospital ColoradoCollaborator
Brigham and Women's HospitalCollaborator
Beth Israel Deaconess Medical CenterCollaborator
Thomas Jefferson UniversityCollaborator
References
Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate. [2022]To estimate the efficacy and safety of a novel nonhormonal therapeutic agent, cabergoline, compared with that of the standard clinical therapy, norethindrone acetate (NETA), for the treatment of endometriosis-associated pain in young women with endometriosis.
Novel Medicine for Endometriosis and Its Therapeutic Effect in a Mouse Model. [2020]Current therapeutic medicines for endometriosis cannot be administered during assisted reproductive technology (ART) because they have bad effects during pregnancy. In this study, we created an animal model of endometriosis and evaluated the therapeutic effect of progestin (Dienogest), dopamine agonist (Cabergoline), and their combination (Dienogest + Cabergoline). We established a mouse model mimicking human endometriosis. The mice with endometriosis were then treated with a single drug (Dienogest or Cabergoline) or both drugs (Dienogest + Cabergoline) for 14 days. An immunohistological study was then performed to analyze inflammatory lesions in the recipient mice. Real-time polymerase chain reaction (RT-PCR) and Western blotting were also performed to determine the levels of genes and proteins in inflammatory lesions to assess the recovery of endometriosis. Histologic staining showed that all medication groups showed a clear decrease in the inflammatory phenotype in the uterus, peritoneum, and intestine. Gene and protein expression analysis showed a therapeutic effect in all medication groups. In conclusion, Cabergoline had a therapeutic effect similar to that of Dienogest and could be used as an alternative to Dienogest during ART for patients with infertility; compared to the individual drugs, the combination treatment has a synergistic effect on endometriosis.
The Effects of Micronized Progesterone and Cabergoline On a Rat Autotransplantation Endometriosis Model: A Placebo Controlled Randomized Trial. [2022]The etiology of endometriosis is complex and various theories have been postulated. Endometriosis pathogenesis involves genetic susceptibility, immunologic alterations and inflammatory prerequisite pathways. In this pilot experimental animal study we wanted to investigate the effects of cabergoline and micronized progesterone on a rat endometriosis model.
Cabergoline and hyperprolactinaemia: new preparation. Better than bromocriptine. [2013](1) Cabergoline, a dopamine agonist already marketed in about 40 countries, is indicated in France for the treatment of hyperprolactinaemia (idiopathic or caused by a pituitary microadenoma). The reference drug in this setting is bromocriptine. (2) The clinical file on cabergoline is methodologically sound, albeit limited mainly to women with amenorrhoea. (3) Two partially blinded comparative trials have shown that cabergoline is significantly more effective than bromocriptine in restarting ovulatory cycles with menstruation. (4) In these trials the incidence of nausea was significantly lower on cabergoline than on bromocriptine. Other adverse events seem to be equally frequent with the two drugs. (5) Cabergoline is effective when taken once or twice a week, while bromocriptine needs to be taken several times a day.
The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis. [2019]Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50 ΞΌg/kg per day oral Cb2, or 50 or 200 ΞΌg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.
A cross-over study with the two novel dopaminergic drugs cabergoline and quinagolide in hyperprolactinemic patients. [2018]Cabergoline and quinagolide, two new dopamine agonist drugs with long-lasting activity, are currently under investigation for the treatment of hyperprolactinemia. At present, studies comparing these drugs for tolerability and efficacy in the same patients are lacking. It was our aim to make such a comparison in an open randomized cross-over trial. Cabergoline (0.5 mg twice weekly) and quinagolide (75 micrograms once daily) were given orally. Each drug was administered for 12 weeks. Treatment with the second drug was started after the recurrence of hyperprolactinemia. Twelve women with hyperprolactinemia due to idiopathic disease (n = 6), microprolactinoma (n = 5) or postsurgical empty sella (n = 1) were evaluated. Six women were amenorrheic and 6 were oligomenorrheic. Ten had spontaneous or provoked galactorrhea. Baseline characteristics (age, clinical signs and PRL levels) of patients initially allocated to the two treatment groups were similar. Nine patients completed both treatment cycles and PRL levels were lower under cabergoline (10.7 +/- 3.7 micrograms/L) than under quinagolide (25.0 +/- 7.7 micrograms/L; p
Cabergoline. [2022]Cabergoline (CAB) (1-[(6-allelylergolin-8 beta-yl)carbonyl]-1-[3-(dimethylamino)propyl]-3-ethyl-urea) is an ergoline derivative with potent, selective and long-lasting inhibitory activity on prolactin (PRL) secretion acting on dopamine receptors present in pituitary lactotrophes. Receptor binding studies have demonstrated that CAB has high in vitro selectivity and affinity for the subtype D2 of the dopamine receptor. In cultures of rat anterior pituitary cells, the concentrations of CAB and bromocriptine required to inhibit PRL secretory activity by 50% (IC50) were 0.1 and 3.4 nmol/l, respectively. As compared to bromocriptine, CAB was more potent in inhibiting the binding of [3H]N-n-propylnorapomorphine and it occupied the receptor for longer. These effects were observed in all areas of the rat brain. In vivo, CAB at doses of 0.125-1 mg twice weekly caused a dose-dependent suppression of PRL secretion in women with hyperprolactinaemia. CAB was shown to be significantly more effective than bromocriptine in inducing a complete biochemical response and clinical efficacy and was better tolerated than bromocriptine in the majority of patients. Notable tumour shrinkage until tumour disappearance was observed during CAB treatment in most patients with macroprolactinoma. CAB was also shown to be effective in patients resistant or poorly responsive to bromocriptine. In view of the limited data on CAB-associated pregnancies and the long half-life of the drug, it is currently recommended that women seeking to became pregnant, once ovulatory cycles have been established, should discontinue CAB therapy 1 month before they intend to conceive. However, no data on negative effects on pregnancy or offspring have been reported. The great efficacy of CAB together with its excellent tolerability makes this drug the current treatment of choice for the majority of patients with hyperprolactinaemic disorders. Very recently, the efficacy of CAB treatment has been reported in patients with acromegaly and clinically non-functioning adenomas with controversial results. CAB was also reported to have some efficacy in patients with Nelson's syndrome and Cushing's disease although these data are available only for limited case reports.
Absence of major fibrotic adverse events in hyperprolactinemic patients treated with cabergoline. [2018]Cabergoline, a dopamine agonist used to treat hyperprolactinemia, is associated with an increased risk of fibrotic adverse reactions, e.g. cardiac valvular fibrosis, pleuropulmonary, and retroperitoneal fibrosis.
Effectiveness and tolerability of long term treatment with cabergoline, a new long-lasting ergoline derivative, in hyperprolactinemic patients. [2018]Cabergoline (CAB) is a new oral dopaminergic compound showing a very long-lasting PRL-lowering activity and reported to be well tolerated. The efficacy and tolerability of chronic treatment with CAB in 30 female hyperprolactinemic patients, aged 18-52 yr (6 microadenomas, 3 macroadenomas, and 21 functional hyperprolactinemias), were studied. In a group of 10 patients who received CAB (0.8 mg once weekly or 0.4 mg twice weekly) for 8 weeks PRL levels normalized while on treatment and remained normal (8 patients) or greatly reduced (1 patient) for 1-2 months after discontinuation of the drug. Twenty-six patients underwent chronic treatment (6-12 months) with an initial dose of 0.5 mg once weekly, subsequently increased to 1-2 mg in 10 patients and decreased in the other 2. Due to severe side-effects CAB was discontinued in 3 patients, in 1, 8, and 12 weeks. A significant reduction of PRL levels was already observed after the first week of treatment (mean +/- SEM basal values, 90.1 +/- 13.3 vs. 29.5 +/- 6.3 micrograms/L; P less than 0.001). Twenty-two patients had normal PRL levels in 1-36 weeks (mean, 6 weeks) with 0.5-2 mg CAB. Twenty-two patients resumed regular menses; 2 patients became pregnant after 3-11 months of treatment. Thirteen patients complained of side-effects (nausea, hypotension, headache, gastric pain, dizziness, and weakness) that disappeared with time in 10 of them. The comparison with a previous bromocriptine treatment regimen in 20 patients had shown that the number of patients requiring discontinuation of the latter drug was significantly higher (7 vs. 3 patients; P less than 0.001). However, 2 patients who needed to discontinue CAB were able to tolerate bromocriptine therapy. A computed tomographic scan performed after 12 months of therapy in 7 patients showed a significant reduction (50%) of the adenoma in 5. In conclusion, our results show that CAB is a well tolerated new dopamine agonist with long-lasting activity that represents an advance in chronic medical treatment of hyperprolactinemic conditions.
A practical synthesis of cabergoline. [2019]Cabergoline is an N-acylurea derived from 9,10-dihydrolysergic acid, which is a potent prolactin inhibitor. It is marketed by Pharmacia as Dostinex for the treatment of hyperprolactinemia and is currently under active development for the treatment of a variety of CNS disorders. In the existing process, the N-acylurea is formed by the reaction of an amide with a large excess of ethyl isocyanate at elevated temperatures. An improved process was developed that eliminates this hazardous reaction. The amide is reacted with phenyl chloroformate and then with ethylamine, which provides a mild and efficient means of forming the unsymmetrical N-acylurea.
Effects of cabergoline and dimethylcabergoline on the sexual behavior of male rats. [2023]Cabergoline (CAB) is an ergot derivative typically prescribed for the treatment of hyperprolactinemia. It suppresses the release of prolactin through agonist actions on dopamine (DA) D2 receptors; however, it possesses binding affinity for other DA and 5-HT receptors. Side effects that exacerbate valvular heart disease can occur with high doses.
Effects of the dopamine agonist cabergoline in patients with prolactinoma intolerant or resistant to bromocriptine. [2019]Cabergoline is a new long-acting crgoline derivative used to treat hyperprolactinaemia. Its effect was assessed in 10 patients (eight women and two men) with prolactinoma who were intolerant (group I: N = 7) or resistant (group II: N = 3) to bromocriptine. In group I, no side effect was observed on cabergoline therapy; two patients became pregnant and normoprolactinaemia was achieved in the live others. In group II, cabergoline was active and well-tolerated in two out of the three patients: one woman had three consecutive pregnancies: in another patient normoprolactinaemia was restored and the tumour shrank by 60%; in the third patient cabergoline was discontinued because of side effects and inefficacy. Thus, cabergoline appears to be an alternative of choice as treatment of hyperprolactinaemic patients who are intolerant or resistant to bromocriptine.
[Hyperprolactinemic amenorrhea:treatment with cabergoline versus bromocriptine. Results of a national multicenter randomized double-blind study]. [2022]Cabergoline is a new, long-acting D2 agonist, highly effective in suppressing prolactin and restoring gonadal function in hyperprolactinaemic amenorrhoea. This study compares its efficacity and safety with that of the reference compound, bromocriptine.