Effect of Aminobiphosphonates and Statins on Circulating Vgamma9Vdelta2-T Cells

Bone Metastases of a Malignant Tumor Clinical Trial

Official title:

Effect of Aminobiphosphonates and Statins on Circulating Vgamma9Vdelta2-T Cells

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01179464
• Other study ID #: 2010/70
• Status: Completed
• Phase: N/A
• First received: August 4, 2010
• Last updated: June 13, 2013
• Start date: August 2010
• Est. completion date: May 2013

Study information

• Verified date: May 2013
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Metastases of a Malignant Tumor
• Neoplasms

Intervention

Drug:
• Aminobiphosphonate
Patients will receive standard intravenous biphosphonate treatment
• Simvastatin
40 mg once daily

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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).	5 weeks	No
Primary	Occurrence of a febrile response	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.	2 days	No
Primary	Functional (IFN-?, TNF-a, granzyme B) changes in the circulating pool of Vy9Vd2-T cells.	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-?, TNF-a, granzyme B).	5 weeks	No