An Exploratory SPECT Imaging Study to Assess the Utility of High-specific Activity 99mTc-HMPAO Labeling as a Tool to Detect PBMC and Lymphocyte Trafficking in the Small Bowel or Ileo-caecal Region of Crohn's Disease Patients
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Crohn's Disease
- Sponsor
- GlaxoSmithKline
- Enrollment
- 13
- Locations
- 1
- Primary Endpoint
- Quantification of scintigraphic activity score for small bowel disease (for both PBMC and lymphocyte imaging methodologies)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Quantification of scintigraphic activity score for small bowel disease (for both PBMC and lymphocyte imaging methodologies)
Time Frame: 1 day
Secondary Outcomes
- 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)