Efficacy of Rapid Escalation of Cabergoline in Comparison to Conventional Dosing in Prolactin Secreting Macroadenomas.
Recruitment status was: Recruiting
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Efficacy of Rapid Escalation of Cabergoline in Comparison to Conventional Dosing in Prolactin Secreting Macroadenomas.|
- Normoprolactinemia [ Time Frame: 1 year ] [ Designated as safety issue: No ]Duration for normalization of serum prolactin and decrease in tumor volume >50 % from baseline.
- Duration for resolution of Hypogonadism [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||March 2012|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: Rapid escalation
Weekly escalation of cabergoline dose in macroprolactinomas Start with 1 mg/week. increase by 1mg/wk every week till 4 weeks. after 4 weeks Cabergoline dose would be increased @1mg/wk every 4 weekly till normalization of prolactin and >50% decrease in tumor volume from baseline.
In the Rapid escalation group schedule of cabergoline dosing will be as follows:
Begin with 0.5 mg twice a 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.
Other Name: cabergoline dopamine agonist
Active Comparator: Conventional escalation
Conventional escalation of cabergoline
In the Conventional escalation group schedule of cabergoline dosing will be 0.5 mg once a week for 4 weeks. Cabergoline will be incrementally dose adjusted on the basis of individual Prolactin values till amelioration of hyper prolactinemia @ 0.5 mg/wk every 4 weeks, till 24 weeks or till primary endpoint.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01143584
|Postgraduate Institute of Medical Education and Research|
|Chandigarh, India, 1700112|
|Study Chair:||Anil Bhansali, MD DM||Postgraduate Institute of Medical Education and Research|
|Principal Investigator:||Pinaki Dutta, MD DM||Postgraduate Institute of Medical Education and Research|
|Principal Investigator:||Rama Walia, MD DM||Postgraduate Institute of Medical Education and Research|
|Principal Investigator:||Paramjeet Singh, MD||Postgraduate Institute of Medical Education and Research|
|Principal Investigator:||Vishali Gupta, MS||Postgraduate Institute of Medical Education and Research|
|Principal Investigator:||Rajesh Vijaiwergiya, MD DM||Postgraduate Institute of Medical Education and Research|
|Principal Investigator:||Ashu Rastogi, MD||Postgraduate Institute of Medical Education and Research|
|Principal Investigator:||Naresh Sachdeva, PhD||Postgraduate Institute of Medical Education and Research|