Effect of Aminobiphosphonates and Statins on Circulating Vgamma9Vdelta2-T Cells

This study has been completed.
Sponsor:
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT01179464
First received: August 4, 2010
Last updated: June 13, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to investigate the effects of aminobiphosphonate treatment on the phenotype and function of circulating Vgamma9Vdelta2-T cells and to determine whether these effects are inhibited by simultaneous treatment with statins.


Condition Intervention
Bone Metastases of a Malignant Tumor
Drug: Aminobiphosphonate
Drug: Simvastatin

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Aminobiphosphonates and Statins on Circulating Vgamma9Vdelta2-T Cells

Resource links provided by NLM:


Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • Phenotypic (APC markers: CD1d, CD40, CD80, CD83, CD86, HLA-DR; activation/memory markers: CD25, CD27, CD45RA, CD45RO, CCR7)changes in the circulating pool of Vy9Vd2-T cells. [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
    Peripheral blood mononuclear cells will be isolated from the drawn peripheral blood. Using intra- and extracellular flowcytometry Vy9Vd2-T cells will be characterized phenotypically (APC markers: CD1d, CD40, CD80, CD83, CD86, HLA-DR; activation/memory markers: CD25, CD27, CD45RA, CD45RO, CCR7).

  • Occurrence of a febrile response [ Time Frame: 2 days ] [ Designated as safety issue: No ]
    Patients will be requested to measure their temperature thrice daily during the 2 days following the first aminobisphosponate administration. This, because a relation between the occurrence of a febrile response upon aminobisphosponate administration and an activation and expansion of Vy9Vd2-T cells has been suggested.

  • Functional (IFN-γ, TNF-α, granzyme B) changes in the circulating pool of Vy9Vd2-T cells. [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
    Peripheral blood mononuclear cells will be isolated from the drawn peripheral blood. Using intra- and extracellular flowcytometry Vy9Vd2-T cells will be characterized functionally (IFN-γ, TNF-α, granzyme B).


Enrollment: 19
Study Start Date: August 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aminobiphosphonates
Aminobiphosphonates
Drug: Aminobiphosphonate
Patients will receive standard intravenous biphosphonate treatment
Experimental: Aminobiphosphonates and Statin
Aminobiphosphonates and Statin
Drug: Aminobiphosphonate
Patients will receive standard intravenous biphosphonate treatment
Drug: Simvastatin
40 mg once daily

Detailed Description:

A total of 40 patients will be entered in this study. Half of the patients will receive standard intravenous treatment with aminobsiphosphonates, the other half will be additionally be treated with a statin. Patients already receiving statin treatment will continue this treatment, other patients will be asked whether they are willing to be treated with a statin for a maximum of 5 weeks. Consenting patients will be randomized to receive i.v. aminobisphosponates plus or minus simvastatin 40 mg once daily. Simvastatin will be started one week prior to the first administration of aminobisphosphonates and continued for a maximum of 5 weeks. In each patient 10 ml peripheral blood will be drawn (t=0, t=24 hr, t=1 week, t=3-4 weeks (prior to the 2nd aminobisphosphonate administration). In addition, patients will be requested to measure their temperature thrice daily during the 2 days following the first aminobisphosponate administration. This, because a relation between the occurrence of a febrile response upon aminobisphosponate administration and an activation and expansion of Vy9Vd2-T cells has been suggested. Peripheral blood mononuclear cells will be isolated from the drawn peripheral blood. Using intra- and extracellular flowcytometry Vy9Vd2-T cells will be characterized phenotypically (APC markers: CD1d, CD40, CD80, CD83, CD86, HLA-DR; activation/memory markers: CD25, CD27, CD45RA, CD45RO, CCR7) and functionally (IFN-γ, TNF-α, granzyme B). In addition, the frequency of CD3+, CD4+, CD8+ T cells, NK cells, B cells, iNKT cells, CD4+CD25+ regulatory T cells, and circulating dendritic cells will be assessed.

  Eligibility

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

Inclusion Criteria:

  • Patients with an indication for intravenous treatment with an aminobiphosphonate because of a malignant tumor
  • WHO 0,1,2 performance score

Exclusion Criteria:

  • WHO 3, 4 performance score
  • prior or current use of aminobisphosphonates -immunosuppressive medication (NSAID allowed)
  • chemotherapy and/or radiotherapy in 4 weeks prior to start of aminobisphosphonate administration
  • renal insufficiency (creatinine clearance < 30 ml/min)
  • liver enzyme abnormalities:

    • bilirubin > 1.5 times ULN (upper limit of normal)
    • ASAT or ALAT > 2.5 times ULN (in absence of liver metastases)
    • ASAT or ALAT > 5 times ULN (in presence of liver metastases)
  • concomitant use of strong inhibitors of CYP3A4, such as itraconazole, ketoconazole, erytromycin, clarithromycin, hiv-protease inhibitors or grapefruit juice is contra-indicated.
  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: NCT01179464

Locations
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081HV
Sponsors and Collaborators
VU University Medical Center
Investigators
Principal Investigator: J J van der Vliet, MD, PhD VU University Medical Center
  More Information

No publications provided

Responsible Party: H.M.W. Verheul, MD, PhD, Professor of Medical Oncology, VU University Medical Center
ClinicalTrials.gov Identifier: NCT01179464     History of Changes
Other Study ID Numbers: 2010/70
Study First Received: August 4, 2010
Last Updated: June 13, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Simvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014