Safety and Potency of a High Cabergoline Dosage in Microprolactinomas (SPARAGMOS)

March 10, 2026 updated by: Andrea Glezer, University of Sao Paulo General Hospital
This will be a multicenter, prospective, randomized, open-label trial with women harboring microprolactinomas and treatment naïve. The sample will be added consecutively and randomized into 2 unblinded groups: the high dosage group will receive a high cabergoline (CAB) dose for a period of ~6 months vs the standard dosage group, which will use the lowest needed dose of CAB to achieve normoprolactinemia for 2 years. The primary outcome will be remission rate.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Prolactinoma is the most common subtype of pituitary adenoma, and dopamine agonists are the gold standard for treatment, primarily CAB. The SPARAGMOS trial will be an interventional, randomized, open-label, multicenter study utilizing a high dose of CAB for ~6 months to suppress prolactin levels, with the hypothetical goal of achieving greater tumor apoptosis and remission rates. The control group will receive CAB for two years at the lowest dose necessary to achieve normoprolactinemia, as per current guidelines. Of note, for both groups, the final cumulative dose will be similar. The findings from this trial have the potential to inform and redefine future therapeutic strategies for microprolactinoma.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1. Willing and able to provide written informed consent prior to any study-related procedures
  • 2. Adults >18 years old
  • 3. Pre-menopausal women
  • 4. Presence of signs and symptoms matching prolactinoma
  • 5. Hyperprolactinemia, defined as a prolactin (PRL) level ≥2 times the local laboratory maximum level of normality, present at the time of enrolment
  • 6. Presence of an identifiable pituitary mass on MRI with a maximum diameter of less than 1cm, independently of Knosp/invasiveness of the cavernous sinus
  • 7. Treatment naïve
  • 8. Females who engage in heterosexual intercourse must agree to use either a highly effective or a clinically acceptable method of contraception from the beginning of screening to the last study visit, which will include:
  • Hysterectomy or bilateral salpingectomy
  • Bilateral tubal occlusion or ligation
  • Vasectomized partner
  • Intrauterine device (copper or hormonal)
  • Progestogen-only contraception (oral, injectable or implantable)
  • Male or female condom with or without spermicide
  • Sexual abstinence (only when it is the usual and preferred lifestyle of the subject)

Exclusion Criteria:

  • 1. History of primary hyperparathyroidism
  • 2. Use of combined hormonal contraceptive within the past 4 weeks
  • 3. Pregnancy or current pregnancy desire
  • 4. Prolactinoma associated with a known genetic syndrome
  • 5. Familial history of pituitary adenoma
  • 6. Renal failure (estimated glomerular filtration rate <30 mL/min /1.73m2)
  • 7. IGF-1 level above the age-adjusted normal range of the local laboratory (IGF 1 >1x ULNR)
  • 8. Idiopathic hyperprolactinemia (normal MRI) or presence of macroprolactinemia
  • 9. Concomitant mental condition rendering her unable to understand the nature, scope, and possible consequences of the study, and/or decompensated psychiatric disease (i.e. gambling or severe obsessive-compulsive disorder), as judged by the Investigator
  • 10. Chronic use of drugs related to hyperprolactinemia (such as metoclopramide, methyldopa, ranitidine, and opioid-related analgesics)
  • 11. Resistant prolactinoma, defined as non-normalization of PRL levels with 2mg/w of CAB
  • 12. Patients in the high dosage group who did not use 3.5mg/w of CAB for an entire 6 months (due to intolerance or non-compliance) or failed to achieve the target dose for any other reason
  • 13. Active malignant disease within the last 5 years, except basal and squamous cell carcinoma of the skin with complete local excision
  • 14. Any decompensated chronic condition (i.e. heart failure NYHA 3-4, diabetes with HbA1c >8.5%, hypothyroidism with TSH >10 mIU/L) that, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes
  • 15. Male sex
  • 16. Cushing stigmas (moon face, muscle weakness, red striation) or suspicious
  • 17. Prior radiotherapy of the pituitary gland area for any reason
  • 18. Additional pituitary tumor-directed therapy, including temozolomide, everolimus, lapatinib, or cytotoxic chemotherapy
  • 19. Hepatopathy with AST/TGO or ALT/TGP >3x the upper limit of normality

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Conventional therapy
Drug: Cabergoline
Patients eligible for the study and randomized to the HIGH CAB arm will start oral CAB, 1 pill of 0.5mg, once a week. The dose will be increased by 0.5mg every week until the target dose of 3.5 mg/w. This initial low-dose-escalating regimen of 7 weeks will be used to prevent symptoms of intolerance. When 3.5 mg/w (1 pill every day) is reached, the patient must maintain this dose for 6 months. After this period, a 1-month de-escalation regime is implemented, reducing the dose by 1 mg/w (2 pills per week) until discontinuation.
Drug: Cabergoline
The standard dosage group will receive conventional treatment as recommended by current guidelines: a low dose of CAB enough to achieve normoPRL for 2 years. All patients will start CAB with 1 pill (0.5mg) once a week. The CAB dose can be adjusted during visits if hyperPRL is not resolved (maximum dose 2mg/w to prevent inclusion of resistant cases). The expected dose used for this arm during follow-up is between 0.5 and 1 mg/w. After completion of 2 years of treatment, all patients will have CAB withdrawn, irrespective of tumor reduction, PRL levels or last CAB dose used.
Experimental: HIGH CAB dose
Drug: Cabergoline
Patients eligible for the study and randomized to the HIGH CAB arm will start oral CAB, 1 pill of 0.5mg, once a week. The dose will be increased by 0.5mg every week until the target dose of 3.5 mg/w. This initial low-dose-escalating regimen of 7 weeks will be used to prevent symptoms of intolerance. When 3.5 mg/w (1 pill every day) is reached, the patient must maintain this dose for 6 months. After this period, a 1-month de-escalation regime is implemented, reducing the dose by 1 mg/w (2 pills per week) until discontinuation.
Drug: Cabergoline
The standard dosage group will receive conventional treatment as recommended by current guidelines: a low dose of CAB enough to achieve normoPRL for 2 years. All patients will start CAB with 1 pill (0.5mg) once a week. The CAB dose can be adjusted during visits if hyperPRL is not resolved (maximum dose 2mg/w to prevent inclusion of resistant cases). The expected dose used for this arm during follow-up is between 0.5 and 1 mg/w. After completion of 2 years of treatment, all patients will have CAB withdrawn, irrespective of tumor reduction, PRL levels or last CAB dose used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission
Time Frame: 3, 6 and 12 months after treatment
Compare laboratory and clinical recurrence of hyperPRL at 3, 6 and 12 months after CAB treatment in the high dosage group vs the standard dosage group (conventional treatment). Laboratory recurrence will be characterized after withdrawal from CAB treatment by the presence of PRL levels above 2x the normal upper limit of reference, after a previous period where PRL levels were within the normal range. At least two separate serum samples are needed to confirm recurrence. The time between samples will be more than a week to ensure sustained elevation. Clinical recurrence will be defined as the recrudescence of symptomatic hyperPRL.
3, 6 and 12 months after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2026

Primary Completion (Estimated)

August 20, 2027

Study Completion (Estimated)

December 20, 2029

Study Registration Dates

First Submitted

March 4, 2026

First Submitted That Met QC Criteria

March 4, 2026

First Posted (Actual)

March 11, 2026

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 94925726.0.1001.0068 (Other Identifier: CAPPesq)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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