Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS) (HSP-SMP)

August 16, 2016 updated by: Centre Hospitalier Universitaire Dijon

Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS): Fundamental Observational in Vitro Study Using Samples From a Collection

Heat-shock proteins (HSP) have been very highly conserved throughout the evolution of species and are characterized by their chaperone function, thanks to their ability to prevent aggregation and to promote the renaturation/break down of damaged proteins. Among other targets, they also chaperone JAK2, a key step that is deregulated in signalling in myeloproliferative syndromes (MPS) because of the JAK2V617F mutation. These HSP also have a potent cytoprotective action through their multiples inhibiting effects on apoptotic processes.

Little is known about levels of HSP expression, in particular for HSP70 and HSP27, in MPS cells.

However, in vitro studies of different cell models have shown the interest of HSP90 inhibitors in slowing cell proliferation in MPS. These results have been confirmed in animal models with results in terms of blood counts and overall survival. In addition, it seems that the V617F mutated form of JAK2 is more sensitive than the wild-type to HSP90 inhibitors. Finally, inhibitors of HSP90 remain efficacious with regard to the inhibition of cell growth, even in cases of resistance to JAK2 inhibitors. Nonetheless, HSP90 inhibitors are known to stimulate the expression of other HSP, notably HSP27 and HSP70, which are, through their properties, tumorigenic and could lead to an escape phenomenon. Thus the combined use of several HSP inhibitors could be beneficial, and eventually present synergistic effects on the inhibition of tumour processes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

37

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

  • France
      • Dijon, France, 21079
        • CHU Dijon Bourgogne

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with Myeloproliferative Syndrom

Description

Inclusion Criteria:

MPS Patients:

  • Patients with MPS
  • Patients who have been informed and not objected to the tests
  • Patients over 18 years old
  • Patients whose samples have been preserved at the CRB in the "Haemopathies" collection

Control patients:

  • Patients over 18 years old
  • Pregnant patients
  • Patients who have been informed and not objected to the collection of their cord blood after the delivery

Exclusion Criteria:

  • Adults under guardianship

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Control
Biological: Blood sample
Other: Flow cytometry
Other: western blot
MPS
Biological: Blood sample
Other: Flow cytometry
Other: western blot

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparing the level of expression of HSP (HSP90, HSP70, HSP27) between cells from a collection of samples of patients with myeloproliferative disease and healthy controls .
Time Frame: through study completion, an average of 1 year
Level of protein expression using flow cytometry and western blot
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Cell death after in vitro treatment with different HSP inhibitors
Time Frame: through study completion, an average of 1 year
through study completion, an average of 1 year

Collaborators and Investigators

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

Sponsor

Centre Hospitalier Universitaire Dijon

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

January 1, 2015

Primary Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

August 4, 2016

First Submitted That Met QC Criteria

August 16, 2016

First Posted (Estimate)

August 22, 2016

Study Record Updates

Last Update Posted (Estimate)

August 22, 2016

Last Update Submitted That Met QC Criteria

August 16, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIRODON 2014

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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