PBMC (Peripheral Blood Mononuclear Cells) /Lymphocyte SPECT (Single Photon Emission Computerized Tomography) Imaging in Crohn's Disease
- Conditions
- Crohn's Disease
- Interventions
- Other: Labeling Ceretec
- Registration Number
- NCT01051622
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Using scintigraphic imaging including planar scintigraphy and SPECT, this study will evaluate the utility of two different ex vivo 99mTc-HMPAO labelled mononuclear cell populations in order to select the optimal methodology (using PBMC or purified lymphocyte subpopulations) for future drug intervention studies in Crohn's disease.
Two parallel exploratory approaches will be investigated to enrich for lymphocyte populations expressing leukocyte trafficking inhibitors. In the first, whole blood will be fractionated on a ficoll gradient to purify a heterogeneous population of all the peripheral blood mononuclear cells (PBMC) for labelling. Secondly, further enrichment will be attempted using depletion of PBMC fractions of monocytes and B cells.
- Detailed Description
This study is based on the established technology of scintigraphic 'white cell scanning', in which the leukocytes in a limited volume of patient's blood are radiolabeled with indium-111 or technetium-99m, re-introduced into the circulation, and their subsequent trafficking and accumulation in areas of active inflammation is visualised by scintigraphic imaging. This methodology is routinely used for diagnosis of inflammatory conditions and pharmacodynamic changes have been documented in the literature. As it is intended that this technology could be used in future drug intervention studies.
However, because this sub-population labelling methodology remains exploratory, this study will investigate the utility of such techniques for use in future clinical trials in Crohn's patients.
Two parallel exploratory approaches will be investigated to enrich for lymphocyte populations expressing leukocyte trafficking inhibitors. In the first, whole blood will be fractionated on a ficoll gradient to purify a heterogeneous population of all the peripheral blood mononuclear cells (PBMC) for labelling. Secondly, T lymphocytes will be further enriched by depletion of monocytes and B cells from PBMC fractions. In part A one scintigraphy scan will be performed in healthy volunteers to confirm that the purification and labelling procedure does not show abnormal biodistribution compared to the known physiological distribution of labelled mononuclear cells \[Bennink, 2008\].
In part B, Crohn's disease patients will then be recruited to undergo two scintigraphy scans 48-72 hours apart to establish intra-patient variability and feasibility of the repeated procedure that will be used in subsequent studies for therapeutic intervention. Analysis of SPECT images will be performed using a standardized scoring system.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 13
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PBMC Trafficking Labeling Ceretec In part B, Patients undergo a blood draw (up to150 mL) and the PBMC's are separated and selected or 99mTc-HMPAO labeling. The purified and labelled cells will be re-introduced into the patient by intravenous infusion and one SPECT scan and up to 8 serial planar scintigraphy scans will initially be conducted over up to 6 hours within 1 scan session. All suitable patients showing evidence of cellular uptake in the ileo-caecal region and/or small bowel at Visit 1 will be progressed to an identical second cell labeling and scanning session at Visit 2 (48 hours later). Subjects showing no evidence of cellular uptake in the ileo-caecal region or small bowel at Visit 1 (negative scan) will be withdrawn from the study and proceed to the follow-up. T Lymphocyte Trafficking Labeling Ceretec In part B, Patients undergo a blood draw (up to150 mL) and the T lymphocyte cells are separated and selected or 99mTc-HMPAO labeling. The purified and labelled cells will be re-introduced into the patient by intravenous infusion and one SPECT scan and up to 8 serial planar scintigraphy scans will initially be conducted over up to 6 hours within 1 scan session. All suitable patients showing evidence of cellular uptake in the ileo-caecal region and/or small bowel at Visit 1 will be progressed to an identical second cell labeling and scanning session at Visit 2 (48 hours later). Subjects showing no evidence of cellular uptake in the ileo-caecal region or small bowel at Visit 1 (negative scan) will be withdrawn from the study and proceed to the follow-up. visit.
- Primary Outcome Measures
Name Time Method Quantification of scintigraphic activity score for small bowel disease (for both PBMC and lymphocyte imaging methodologies) 1 day
- Secondary Outcome Measures
Name Time Method Circulating PBMC and lymphocyte subpopulation cell counts and correlation with scintigraphic activity scores. 1 day Tolerability endpoints including AEs Up to 3 weeks Variability and reproducibility of the PBMC and lymphocyte imaging methodologies at visits 1 and 2. Up to 3 days Rate of label accumulation in small bowel 1 day Correlation between CDAI, CRP, calprotectin, ASCA antibodies and SAS Up to 3 weeks
Trial Locations
- Locations (1)
GSK Investigational Site
🇳🇱Amsterdam, Netherlands