Efficacy of Rapid Escalation of Cabergoline in Comparison to Conventional Dosing in Prolactin Secreting Macroadenomas.

Macroprolactinoma Clinical Trial

Official title:

Efficacy of Rapid Escalation of Cabergoline in Comparison to Conventional Dosing in Prolactin Secreting Macroadenomas.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01143584
• Other study ID #: prlcab2020
• Status: Recruiting
• Phase: N/A
• First received: June 1, 2010
• Last updated: June 11, 2010
• Start date: May 2010
• Est. completion date: March 2012

Study information

• Verified date: May 2010
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Anil Bhansali, MD DM
• Phone: 2756583
• Email: anilbhansali_endocrine[@]rediffmail.com
• Is FDA regulated: No
• Health authority: India: Indian Council of Medical Research
• Study type: Interventional

Clinical Trial Summary

To study the effects of rapid escalation of Cabergoline in comparison to conventional dosing in macroprolactinomas. Rapid escalation of cabergoline may help in earlier normalization of prolactin and shrinkage of tumor mass, and thus decrease the cumulative dose of cabergoline altogether.

Description:

The efficacy of cabergoline is dose related and determined by percentage of Dopamine 2 receptor occupancy and prolonged receptor affinity. Activation of membrane receptors and target cell responses is proportional to the degree of receptor occupancy. Greater the drug concentration, greater is the binding and receptor occupancy and greater is the efficacy of the drug. Receptor occupancy can be increased either by using high dose of cabergoline or by rapid escalation of cabergoline. The patients, who respond to increasing dosages of cabergoline, probably do so by increased receptor occupancy with higher doses.

Rapid escalation of doses of cabergoline is another approach to increase the drug concentration and increase the occupancy of the receptor. Earlier decrease in serum prolactin levels with rapid escalation may help in reducing the cumulative dose of cabergoline and total duration of treatment. Though studies with high doses of cabergoline have been performed in prolactinomas with normalization of prolactin levels in almost 100%, but systematic studies using rapid escalation of cabergoline in prolactinomas are lacking except the one by Bhansali et al. In their study, serum prolactin became normal in 93 per cent of the patients with a mean duration of 8.2 wk. The mean decrease in serum prolactin was 99 per cent by four weeks, however a similar decrease (93 to 99%) in prolactin was achieved in other studies with a time lag of 48 to 160 wk. This supports the notion that rapid hike in doses of cabergoline decreases serum prolactin levels faster and it becomes normal in the majority of patients earlier6. However it was an uncontrolled study with limited number of subjects.

Therefore present study was planned to study the efficacy of rapid escalation of Cabergoline versus conventional dosing in patients with macroprolactinomas. Rapid escalation of cabergoline dose may help in earlier normalization of prolactin and shrinkage of tumor mass, and thus decrease the cumulative dose of cabergoline altogether.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Males or females presenting with

1. Prolactin secreting macroadenomas (=10 mm maximum diameter)

2. With/without visual complaints

3. With /without parasellar or suprasellar extension

4. Treatment Naïve

Exclusion Criteria:

1. On treatment with dopamine agonists.

2. Taking other drugs influencing prolactin Levels.

3. Systemic disease like Chronic Kidney Disease, Chronic Lung Disease

4. Other secondary causes of hyperprolactinemia.

5. Prolactin secreting microadenomas

6. Pregnancy during follow up

7. Prolactinoma as part of MEN-1 Syndrome

8. History suggestive of recent apoplexy (3 months)

9. Contraindication to cabergoline therapy like pre existing psychosis.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Macroprolactinoma

Intervention

Drug:
• Cabergoline
In the Conventional escalation group Cabergoline 0.5 mg once a week for 4 weeks and further will be incrementally dose adjusted on the basis of individual PRL values until amelioration of hyper prolactinemia @ 0.5 mg/wk every 4 weeks, till 24 weeks or until primary endpoint. Cabergoline will be maintained at the dose at which PRL will be first normalized till primary end point.
• cabergoline
In the Rapid escalation group schedule of cabergoline dosing will be as follows: Begin with 0.5 mg twice a week mg twice a week - second week 1.5 mg twice a week - third week mg twice a week - fourth week 4mg/wk would be continued for next 4 weeks. If prolactin does not normalize by 8 weeks, a repeat hike in dose of 1mg/wk will be done every 4 weekly until normalization of prolactin levels and also >50% decrease in tumor volume. Ceiling dose of Cabergoline will be 12mg/wk.

Locations

Country	Name	City	State
India	Postgraduate Institute of Medical Education and Research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Normoprolactinemia	Duration for normalization of serum prolactin and decrease in tumor volume >50 % from baseline.	1 year	No
Secondary	Duration for resolution of Hypogonadism	Duration for resolution of hypogonadism in males as defined by normal serum total testosterone 9.9-27.8nmol/L and aging male study score(AMS). In females duration to acheive regular menstrual cycles.	1 year	No