Involvement of Endogenous Digitalis-like Compounds in Breast Cancer

April 7, 2011 updated by: Hadassah Medical Organization

The endogenous digitalis-like compounds (DLC)are steroid hormones synthesized and released from the adrenal gland.They are integrated in the feed-back system of the Hypothalami-Pituitary-Adrenal gland axis.One of their remarkable function is to induce apoptosis in malignant cells. Recently, accumulating data point to the possibility of using synthetic DLC as new anti-cancer drugs. Less is known about the endogenous metabolism of these compounds in cancer patients.

Proceeding from preliminary clinical data which demonstrated significantly reduced DLC plasma levels in breast cancer patients and from in vitro data which showed an impaired release of DLC towards stress stimuli in athymic nude mice,we put up the hypothesis that a latent adrenal insufficiency with low DLC levels facilitates the induction and progression of tumor diseases.

Study Overview

Status

Withdrawn

Conditions

Detailed Description

To pursue this question about endogenous DLC metabolism in cancer patients we intend to start with the measurement of DLC plasma levels in breast cancer patients at the time of first diagnosis and compare them to women with benign breast disease as well as healthy women.

Aim of the Study

  • To evaluate the basal DLC plasma concentrations in cancer patients at the time of first diagnosis and the function of the HPA axis, with focussing on breast cancer patients.
  • To analyze a potential change of HPA function and, in parallel, DLC plasma concentrations in the course of therapy, with special respect to treatment failure.
  • To establish a potential correlation between DLC plasma concentrations and risk factors in BC.

Patients and Methods

Patients:

I. 50 - (100) patients with breast cancer at the time of first diagnosis

II. 50 - (100) patients with a benign disease of the breast

III. 50 - (100) women undergoing plastic surgery of the breast

IV. 50 - (100) women who need no further exploration after visit in ambulance (=normal population)

V. additionally a group of 25 - 50 students (age 20-40) will be analyzed in a pilot study

Methods:

Time-schedule for Group I (Group II. - IV. alike, according to disease and/or situation)

  • Day of first presentation of the woman at the clinic
  • Day of first diagnosis, i.e. biopsy/FNA
  • Day of start of treatment: operation, chemo-/radiotherapy (tst = 0)
  • Day + 30, + 60, + 90
  • 6 month and 1 year after start of treatment

The Group V. (students) will be analyzed in a special schedule, preceding the study 1-2 months:

  • 4 weeks before an important exam
  • a day before the exam (-3 days)
  • a day after the exam (+ 3 days)
  • 2 weeks after the exam
  • 6 weeks after the exam

Parameters

Biochemistry (Group I. - V.)

  • Basal DLC plasma concentration
  • Basal serum Cortisol concentration
  • Basal plasma ATCH concentration
  • Basal Aldosterone/Renin concentration
  • Electrolytes (potassium, sodium, calcium, chloride)

Pathology/Immunohistochemistry (Group I. + II., when benign, including last 4 points)

  • Tumor size
  • lymph node status
  • E/P receptors
  • Grade
  • HER2/neu
  • Bcl-2
  • Ki67
  • p53

Radiology (Group I.)

If abdominal CT available measurement of size of the adrenal glands

Endocrinologic tests (Group I. - IV.)

  • Dexamethasone-test (low dose):

    • 2 mg Dexamethasone p.o. at 24:00
    • measurement of Cortisol and DLC at 8:00 the next morning

  • ACTH-test:

    • basal plasma concentrations of Cortisol, DLC and ACTH
    • administration of 250 µg ACTH (Synachten®) i.v.
    • measurement of Cortisol and DLC after 30 min. and 60 min.
  • Facultative: Metapyrone test

at following time intervals:

  1. Dexamethasone-test

    • around the time of first presentation (± 5 days)
    • around the time of start of treatment (± 5 days); corresponding times for Group II.- IV.
    • Day + 30, +60, +90
    • 6 month and a year after start of treatment

  2. ACTH-test

    • On the day of first presentation
    • On the day of start of treatment; corresponding times for Group II.- IV.
    • Day + 30, +60, +90
    • 6 months and one year after start of treatment

Psychometric test for Stress Evaluation (Group I. - V.)

  • at the day of first presentation (Students: in between the last 2 weeks before an exam)
  • at the end of the study

Study Type

Observational

Enrollment (Anticipated)

250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Jerusalem, Israel
        • Hadassah hebrew university medical centers

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Women with first diagnosis of Breast Cancer or a benign Breast Disease

Description

Inclusion Criteria:

  • first visit to a Breast Disease Ambulance for consultation
  • no pregnancy

Exclusion Criteria:

  • no severe heart disease (EF > 40%)
  • no therapy with digitalis
  • no acute/chronic inflammatory disease (e.g. RA, M. Crohn)
  • no dysfunction of the Hypothalamo-Pituitary-Adrenal system
  • no severe mental disorder

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hadassah Medical Organization

Investigators

  • Principal Investigator: Heidrun Weideman, Hadassah hebrew university medical centers

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Study Completion (Anticipated)

May 1, 2008

Study Registration Dates

First Submitted

April 4, 2006

First Submitted That Met QC Criteria

April 4, 2006

First Posted (Estimate)

April 5, 2006

Study Record Updates

Last Update Posted (Estimate)

April 8, 2011

Last Update Submitted That Met QC Criteria

April 7, 2011

Last Verified

May 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 297-31.3-06-HMO-CTIL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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