Treatment of Hyperprolactinemia With the Non-ergoline Dopamine Agonist Ropinirole

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03038308
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 16
• Location: 1
• Arm: 1
• Actual Duration (Months): 49.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperprolactinemia; Prolactinoma	Drug: Ropinirole	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: 1) Forced titration dose response PKPD study and 2) A prospective open-label outpatient dose escalation trial of ropinirole for treatment of prolactinomas and hyperprolactinemia.Forced titration dose response PKPD study and 2) A prospective open-label outpatient dose escalation trial of ropinirole for treatment of prolactinomas and hyperprolactinemia.
• Masking: None (Open Label)
• Masking Description: Open-label studies
• Primary Purpose: Treatment
• Official Title: Treatment of Hyperprolactinemia With the Non-ergoline Dopamine Agonist Ropinirole: A Dose Escalation Study of Efficacy and Tolerability
• Actual Study Start Date: Sep 16, 2016
• Actual Primary Completion Date: Nov 5, 2020
• Actual Study Completion Date: Nov 5, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects That Achieved Stable PRL Normalization [6-12 months]

   Serum prolactin concentrations (PRL levels) were measured in patients at baseline and at follow-up.

Secondary Outcome Measures

1. Number of Subjects With Unchanged Tumor Size [6-12 months]

   Radiologic assessment of tumor size before and after treatment will be made by MRI.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Gabrielle Page-Wilson, M.D., Columbia University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 5, 2019

More Information

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.

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT03038308
• Other Study ID Numbers: AAAI8604; 1R21DK112093-01
• First Posted: Jan 31, 2017
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Columbia University: ropinirole; hyperprolactinemia; prolactin
• Additional relevant MeSH terms: Prolactinoma; Hyperprolactinemia; Ropinirole

Study Results

Participant Flow

Pre-assignment Detail	1 Subject was determined to be ineligible after consenting.

Arm/Group Title	ROP Intervention
Arm/Group Description	Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole
Period Title: Overall Study
STARTED	15
COMPLETED	11
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	ROP Intervention
Arm/Group Description	Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 93.8%
>=65 years	1 6.3%
Sex: Female, Male (Count of Participants)
Female	16 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 18.8%
Not Hispanic or Latino	13 81.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 37.5%
White	10 62.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Data for 10 out of 11 completers were included in this analysis.

Arm/Group Title	ROP Intervention
Arm/Group Description	Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole
Measure Participants	10
Number [percentage of participants]	50 312.5%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data for 8 out of 11 completers with prolactinomas were included in this analysis.

Arm/Group Title	ROP Intervention
Arm/Group Description	Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole
Measure Participants	8
Count of Participants [Participants]	7 43.8%

Adverse Events

Time Frame	6 months
Arm/Group Title	ROP Intervention
Arm/Group Description	Patients with hyperprolactinemia were treated with long-term ROP therapy for 6 months in an open-label dose escalation study Ropinirole: 0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole
All Cause Mortality
	ROP Intervention
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	ROP Intervention
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	ROP Intervention
	Affected / at Risk (%)	# Events
Total	8/10 (80%)
General disorders
Fatigue	6/10 (60%)
Nausea	4/10 (40%)
Headache	2/10 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.