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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2010 by Postgraduate Institute of Medical Education and Research.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier:
NCT01143584
First received: June 1, 2010
Last updated: June 11, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention
Macroprolactinoma
Drug: Cabergoline
Drug: cabergoline

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Postgraduate Institute of Medical Education and Research:

Primary Outcome Measures:
  • Normoprolactinemia [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Duration for normalization of serum prolactin and decrease in tumor volume >50 % from baseline.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 20
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)
Arms Assigned Interventions
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.
Drug: cabergoline

In the Rapid escalation group schedule of cabergoline dosing will be as follows:

Begin with 0.5 mg twice a week

  1. mg twice a week - second week 1.5 mg twice a week - third week
  2. 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.

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.

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.

Other Name: cabergoline

Detailed 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01143584

Contacts
Contact: Anil Bhansali, MD DM 2756583 anilbhansali_endocrine@rediffmail.com
Contact: Ashu Rastogi, MD 09781001046 drpaed@rediffmail.com

Locations
India
Postgraduate Institute of Medical Education and Research Recruiting
Chandigarh, India, 1700112
Contact: Anil Bhansali, MD DM    2756583    anilbhansali_endocrine@rediffmail.com   
Contact: Ashu Rastogi, MD    09781001046    drpaed@rediffmail.com   
Principal Investigator: Anil Bhansali, MD DM         
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
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
  More Information

No publications provided by Postgraduate Institute of Medical Education and Research

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anil Bhansali, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT01143584     History of Changes
Other Study ID Numbers: prlcab2020
Study First Received: June 1, 2010
Last Updated: June 11, 2010
Health Authority: India: Indian Council of Medical Research

Keywords provided by Postgraduate Institute of Medical Education and Research:
Prolactin
Cabergoline
Macroadenomas
escalation

Additional relevant MeSH terms:
Cabergoline
Dopamine Agonists
Anti-Dyskinesia Agents
Antineoplastic Agents
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014