Effect of Aminobiphosphonates and Statins on Circulating Vgamma9Vdelta2-T Cells

NCT01179464 | Completed

• 1 other identifier: 2010/70
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bone Metastases of a Malignant Tumor

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• Functional (IFN-γ, TNF-α, 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-γ, TNF-α, granzyme B).

  5 weeks

Study Arms (2)

Aminobiphosphonates

ACTIVE COMPARATOR

Aminobiphosphonates

Drug: Aminobiphosphonate

Aminobiphosphonates and Statin

EXPERIMENTAL

Aminobiphosphonates and Statin

Drug: Aminobiphosphonate; Drug: Simvastatin

Interventions

Aminobiphosphonate DRUG

Patients will receive standard intravenous biphosphonate treatment

Aminobiphosphonates; Aminobiphosphonates and Statin

Simvastatin DRUG

40 mg once daily

Aminobiphosphonates and Statin

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, 1081HV, Netherlands

Location

MeSH Terms

Interventions

Simvastatin

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• J J van der Vliet, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 4, 2010
• First Posted: August 11, 2010
• Study Start: August 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 14, 2013

Record last verified: 2013-05

Locations

NL (1)