Hyperprolactinemia, Prolactinoma
Conditions
Keywords
ropinirole, hyperprolactinemia, prolactin
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.
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.
Interventions
DRUGRopinirole
0.25mg/day - 6.0mg/day oral non-ergoline dopamine agonist ropinirole
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label studies
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects That Achieved PRL Normalization as Defined by a Serum Prolactin Level Less Than 25ng/mL at Any Time Point During the Study Treatment Period. | 6-12 months | Serum prolactin concentrations (PRL levels) were measured in patients at baseline, 2 and 4 weeks after starting therapy and then once monthly thereafter for 24 weeks. Serum prolactin was measured in duplicate by two-site chemiluminescent enzyme immunometric assay using the Immulite 1000 Analyzer (Siemens Healthcare Diagnostics, Deerfield, IL). The reference range for serum prolactin is 1.9-25 ng/ml for adult females. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Stable or Decreased Tumor Size | 6 months | Number of subjects with stable or decreased tumor size from baseline assessment to assessment after 6 months of treatment. Radiologic assessment of tumor size before and after treatment will be made by MRI. |
Countries
United States
Participant flow
Pre-assignment details
1 Subject was determined to be ineligible after consenting.
Participants by arm
| Arm | Count |
|---|---|
| ROP Intervention 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 | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Surgical resection | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | ROP Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Prolactin | 126 ng/mL STANDARD_DEVIATION 41.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 8 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Percentage of Subjects That Achieved PRL Normalization as Defined by a Serum Prolactin Level Less Than 25ng/mL at Any Time Point During the Study Treatment Period.
Serum prolactin concentrations (PRL levels) were measured in patients at baseline, 2 and 4 weeks after starting therapy and then once monthly thereafter for 24 weeks. Serum prolactin was measured in duplicate by two-site chemiluminescent enzyme immunometric assay using the Immulite 1000 Analyzer (Siemens Healthcare Diagnostics, Deerfield, IL). The reference range for serum prolactin is 1.9-25 ng/ml for adult females.
Time frame: 6-12 months
Population: Of the 16 subjects enrolled, 1 was deemed ineligible after completion of screening, 2 relocated out of state prior to taking first dose, 1 was withdrawn after week 1 following decision to pursue surgical resection of the prolactinoma. 12 participated longitudinally -- 1 was lost to follow-up after 16 weeks; 11 subjects completed 24 weeks and 5/11 subjects continued ropinirole therapy for one year with 2/11 remaining in protocol for 17 months due pandemic related delays in final visits.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ROP Intervention | Percentage of Subjects That Achieved PRL Normalization as Defined by a Serum Prolactin Level Less Than 25ng/mL at Any Time Point During the Study Treatment Period. | 6 Participants |
Secondary
Number of Subjects With Stable or Decreased Tumor Size
Number of subjects with stable or decreased tumor size from baseline assessment to assessment after 6 months of treatment. Radiologic assessment of tumor size before and after treatment will be made by MRI.
Time frame: 6 months
Population: Nine participants analyzed as only 9 participants had a followup MRI at 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ROP Intervention | Number of Subjects With Stable or Decreased Tumor Size | 7 participants |