Involvement of Endogenous Digitalis-like Compounds in Breast Cancer

Sponsor

Hadassah Medical Organization (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00310882

Collaborator

(none)

250

Enrollment

Location

Duration (Months)

10.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms Fibrocystic Disease of Breast Mammaplasty

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:

50 - (100) patients with breast cancer at the time of first diagnosis
50 - (100) patients with a benign disease of the breast
50 - (100) women undergoing plastic surgery of the breast
50 - (100) women who need no further exploration after visit in ambulance (=normal population)
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:

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

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 Design

Study Type:

Observational

Anticipated Enrollment :

250 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Involvement of Endogenous Digitalis-like Compounds in Breast Cancer

Study Start Date :

May 1, 2006

Anticipated Study Completion Date :

May 1, 2008

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hadassah Hebrew University Medical Centers	Jerusalem		Israel

Sponsors and Collaborators

Hadassah Medical Organization

Investigators

Principal Investigator: Heidrun Weideman, Hadassah Hebrew University Medical Centers

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00310882

Other Study ID Numbers:

297-31.3-06-HMO-CTIL

First Posted:

Apr 5, 2006

Last Update Posted:

Apr 8, 2011

Last Verified:

May 1, 2008

Keywords provided by , ,

breast cancer

digitalis like compounds

prognostic factor

Additional relevant MeSH terms:

Breast Neoplasms

Cystic Fibrosis

Fibrocystic Breast Disease

Breast Diseases

Study Results

No Results Posted as of Apr 8, 2011