Treatment of Hyperprolactinemia With the Non-ergoline Dopamine Agonist Ropinirole

Treatment of Hyperprolactinemia With the Non-ergoline Dopamine Agonist Ropinirole: A Dose Escalation Study of Efficacy and Tolerability

The purpose of this study is to evaluate the use of the non-ergoline dopamine agonist ropinirole for the treatment of hyperprolactinemia in patients with idiopathic hyperprolactinemia and prolactinomas.

Study Overview

• Status: Completed
• Conditions: Prolactinoma; Hyperprolactinemia
• Intervention / Treatment: Drug: Ropinirole

Detailed Description

Treatment of prolactin secreting pituitary tumors with traditional ergot dopamine agonist drugs can be limited by medication side effects, pharmacologic resistance, and by concerns regarding the potential risk of cardiac valve disease. The overall goal of this project is therefore to evaluate, for the first time, the efficacy and tolerability of the selective D2/D3 receptor non-ergot dopamine agonist ropinirole for the treatment of prolactinomas. This proposal will establish the pharmacologic profile of this medication when used to treat hyperprolactinemia in patients with prolactinomas and will determine the impact of long-term ropinirole administration on critical clinical parameters including serum prolactin levels, gonadal function, and tumor regression, in order to establish ropinirole's utility as a new, clinically efficacious, safer and more tolerable therapeutic option for the treatment of prolactinomas that may prove particularly useful in patients with underlying cardiac valve disease and in those with resistance or intolerance to ergot dopamine agonists.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 18-70 years
• Prolactin level (PRL) ≥2 times upper limit of normal
• Pituitary adenomas on MRI ≤ 1.5cm in greatest diameter and ≥ 5mm from the optic chiasm
• Normal renal and liver function
• Agrees to barrier contraception if pre-menopausal

Exclusion Criteria:

• Use of medications known to interfere with PRL secretion and PRL and Ropinirole (ROP) metabolism
• Use of another dopamine agonist during the 4 weeks prior
• Pituitary stalk compression on MRI
• History of visual field abnormalities or previous radiation
• Untreated hypothyroidism
• Consumption of > 2 alcoholic drinks per day
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ROP Intervention; Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study	Drug: Ropinirole; 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole; Other Names: ROP therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects That Achieved Stable PRL Normalization	Serum prolactin concentrations (PRL levels) were measured in patients at baseline and at follow-up.	6-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Unchanged Tumor Size	Radiologic assessment of tumor size before and after treatment will be made by MRI.	6-12 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Gabrielle Page-Wilson, M.D., Columbia University

Publications and helpful links

General Publications

• Liu S, Hu C, Peters J, Tsang A, Cremers S, Bies R, Page-Wilson G. Pharmacokinetics and pharmacodynamics of ropinirole in patients with prolactinomas. Br J Clin Pharmacol. 2019 Feb;85(2):366-376. doi: 10.1111/bcp.13802. Epub 2018 Nov 22.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2016
• Primary Completion (Actual): November 5, 2020
• Study Completion (Actual): November 5, 2020

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: January 30, 2017
• First Posted (Estimate): January 31, 2017

Study Record Updates

• Last Update Posted (Actual): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 9, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: ropinirole; hyperprolactinemia; prolactin
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Adenoma; Pituitary Neoplasms; Prolactinoma; Hyperprolactinemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Ropinirole
• Other Study ID Numbers: AAAI8604; 1R21DK112093-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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.: No