PBMC (Peripheral Blood Mononuclear Cells) /Lymphocyte SPECT (Single Photon Emission Computerized Tomography) Imaging in Crohn's Disease

NCT01051622 | Completed Phase 1

• 1 other identifier: 113265
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 2

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.

Conditions

Crohn's Disease

Keywords

PBMC (Peripheral Blood Mononuclear Cells); Crohn's Disease; SPECT (Single Photon Emission Computerized Tomography)

Outcome Measures

Primary Outcomes (1)

• Quantification of scintigraphic activity score for small bowel disease (for both PBMC and lymphocyte imaging methodologies)

  1 day

Secondary Outcomes (5)

• 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

• Circulating PBMC and lymphocyte subpopulation cell counts and correlation with scintigraphic activity scores.

  1 day

• Correlation between CDAI, CRP, calprotectin, ASCA antibodies and SAS

  Up to 3 weeks

Study Arms (2)

PBMC Trafficking

EXPERIMENTAL

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.

Other: Labeling Ceretec

T Lymphocyte Trafficking

EXPERIMENTAL

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.

Other: Labeling Ceretec

Interventions

Labeling Ceretec OTHER

Technetium-99m is used to radiolabel cells of interest i.e PBMC's

PBMC Trafficking; T Lymphocyte Trafficking

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A only:
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, ECG, complete blood count and clinical chemistry. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Part A and B:
• Male or female over 18 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Part B only:
• A history of CD for at least 3 months with a diagnosis confirmed by radiologic, endoscopic or histological assessment.
• Moderate to severe CD as evidenced by an elevated retrospective CDAI score (of
• ≥150) and 1 or more of the following:
• CRP (of ≥5 mg/L); or
• recent (within 4 weeks before the screening visit) evidence of active CD by CT scan, MRI scan or endoscopy. Scans must be part of the patients routine care and should not be conducted as a screening test for this study.
• Radiographic (barium, CT, MRI) or endoscopic evidence of small bowel involvement (if a patient has had a surgical intervention, evidence of small bowel involvement must have been obtained after the procedure).

You may not qualify if:

• Part A and B:
• Known or positive infection with hepatitis B, hepatitis C or HIV.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to Day 1 of the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Part B only:
• Patients with active Crohn's disease with small bowel involvement who are not yet receiving treatment for whom it is judged inappropriate to defer initiating steroid or other treatment for up to 13 days (the maximum interval from screening to last imaging session).
• Patients who are corticosteroid dependent for whom it is judged inappropriate to defer increasing the dose of steroids or initiating other treatment for up to 13 days (the maximum interval from screening to last imaging session).
• Patients who are refractory to steroids or immunosuppressants or anti-TNFs for whom it is judged inappropriate to defer change of medical management or surgical intervention for up to 13 days (the maximum interval from screening to last imaging session).
• The subject is taking \>20mg/day Prednisolone or a prednisolone equivalent during the 4 weeks prior to screening
• The subject received treatment natalizumab within 12 weeks prior to study entry;
• The subject has Hb\<10 g/l or Lymphocyte count \<10\^9 /l
• Known C. difficile infection, or a clinical suspicion of a pathogenic bowel infection (including significant infection due to fistula).
• Suspected or diagnosed intra-abdominal abscess or bowel perforation
• The subjects has had bowel surgery (other than appendectomy) within 12 weeks prior to randomization or is likely to require abdominal surgery within 1 month of screening
• Concurrent illness, infection or disability (including malignancies or neoplastic disease of the bowel) that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study (e.g., an unstable cardiovascular, autoimmune, renal, hepatic, pulmonary, endocrine, metabolic, gastrointestinal, hematologic, psychiatric or neurological condition).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Amsterdam, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2009
• First Posted: January 18, 2010
• Study Start: January 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: June 2, 2014

Record last verified: 2014-05

Locations

BE (1); NL (1)