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Mucosal Response in Immunocompromised Host (MICH)

This study is currently recruiting participants.
Verified August 2012 by Leiden University Medical Center
Sponsor:
Collaborator:
Crucell B.V., Leiden, the Netherlands
Information provided by (Responsible Party):
Darius Soonawala, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01109914
First received: April 22, 2010
Last updated: August 1, 2012
Last verified: August 2012
History of Changes
  Purpose

The aim of this study is to verify whether vaccination with Dukoral® (SBL Vaccines) induces an immune response in renal transplant recipients on prednisolone in combination with either a calcineurin inhibitor CNI), mycophenolate mofetil (MMF) or an mTOR inhibitor (mTORi).


Condition Intervention Phase
Vaccination
Kidney Transplantation
 Biological: Dukoral
 Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immune Response After Inactivated Oral Cholera Vaccine (Dukoral) in Renal Transplant Recipients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Percentage seroconversion among all renal transplant recipients. [ Time Frame: day 20-22 ] [ Designated as safety issue: No ]
    Seroconversion is defined as a ≥2-fold increase in anti-rCTB IgA and IgG titer, measured by EIA or ≥2-fold increase in IgA- or IgG secretion by PBMCs measured by ELISPOT with a minimum of 10 per 10 million PBMCs.


Secondary Outcome Measures:
  • Group differences in geometric mean antibody titers after vaccination [ Time Frame: day 20-22 ] [ Designated as safety issue: No ]
    post-vaccination anti-rCTB IgA and IgG titers, measured by Enzyme Immuno Assay (EIA); post-vaccination IgA- and IgG secretion by PBMCs measured by Enzyme-Linked ImmunoSPOT (ELISPOT)


Estimated Enrollment: 70
Study Start Date: April 2010
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Renal transplant recipients (mTORi)
Renal transplant recipients using prednisolone and an mTORi (everolimus or sirolimus) but no other immunosuppressive drug.
 Biological: Dukoral

Two oral doses of Dukoral® (SBL Vaccines) will be administered (day 0 and day 14). Each dosage contains 3 ml of suspension in a vial and 5.6 g of effervescent granules in a sachet. Each dosage (3 ml) contains: A total of 100000 million bacteria of the following strains:

  • Vibrio cholerae O1 Inaba, classical biotype (heat inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Inaba, El Tor biotype (formalin inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Ogawa, classical biotype (heat inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Ogawa, classical biotype (formalin inactivated) 25x1000 million bacteria* −Recombinant cholera toxin B subunit (rCTB) 1 mg (produced in V. cholerae O1 Inaba, classical biotype strain 213)
Experimental: Renal transplant recipients (MMF)
Renal transplant recipients using prednisolone and mycophenolate mofetil (MMF) but no other immunosuppressive drug.
 Biological: Dukoral

Two oral doses of Dukoral® (SBL Vaccines) will be administered (day 0 and day 14). Each dosage contains 3 ml of suspension in a vial and 5.6 g of effervescent granules in a sachet. Each dosage (3 ml) contains: A total of 100000 million bacteria of the following strains:

  • Vibrio cholerae O1 Inaba, classical biotype (heat inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Inaba, El Tor biotype (formalin inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Ogawa, classical biotype (heat inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Ogawa, classical biotype (formalin inactivated) 25x1000 million bacteria* −Recombinant cholera toxin B subunit (rCTB) 1 mg (produced in V. cholerae O1 Inaba, classical biotype strain 213)
Experimental: Renal transplant recipients (CNI)
Renal transplant recipients using prednisolone and a calcineurin inhibitor (cyclosporine or tacrolimus) but no other immunosuppressive drug.
 Biological: Dukoral

Two oral doses of Dukoral® (SBL Vaccines) will be administered (day 0 and day 14). Each dosage contains 3 ml of suspension in a vial and 5.6 g of effervescent granules in a sachet. Each dosage (3 ml) contains: A total of 100000 million bacteria of the following strains:

  • Vibrio cholerae O1 Inaba, classical biotype (heat inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Inaba, El Tor biotype (formalin inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Ogawa, classical biotype (heat inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Ogawa, classical biotype (formalin inactivated) 25x1000 million bacteria* −Recombinant cholera toxin B subunit (rCTB) 1 mg (produced in V. cholerae O1 Inaba, classical biotype strain 213)
Experimental: Healthy volunteers
Healthy volunteers (partners, brothers or sisters of the renal transplant recipients).
 Biological: Dukoral

Two oral doses of Dukoral® (SBL Vaccines) will be administered (day 0 and day 14). Each dosage contains 3 ml of suspension in a vial and 5.6 g of effervescent granules in a sachet. Each dosage (3 ml) contains: A total of 100000 million bacteria of the following strains:

  • Vibrio cholerae O1 Inaba, classical biotype (heat inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Inaba, El Tor biotype (formalin inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Ogawa, classical biotype (heat inactivated) 25x1000 million bacteria*
  • Vibrio cholerae O1 Ogawa, classical biotype (formalin inactivated) 25x1000 million bacteria* −Recombinant cholera toxin B subunit (rCTB) 1 mg (produced in V. cholerae O1 Inaba, classical biotype strain 213)

Detailed Description:

BACKGROUND:

LT-ETEC is the most common cause of travelers' diarrhoea. Dukoral® (SBL Vaccines) reduces the severity and duration of LT-ETEC induced diarrhea. Dehydration due to diarrhea poses a risk to the health of renal transplant recipients. Therefore Dukoral may benefit this group of travelers.

AIM OF THIS STUDY:

Primary objective: To verify whether vaccination with Dukoral® (SBL Vaccines) induces an immune response in renal transplant recipients on prednisolone in combination with either a calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil or an mTOR inhibitor (sirolimus or everolimus).

Secondary objective: To evaluate to what extent, the immune response differs, depending on the use of different classes of immunosuppressive drugs (CNI, MMF or mTORi).

STUDY DESIGN:

Single center interventional study.

Population: The population base of the study consists of adult renal transplant recipients who received their transplant at our medical center. The control population consists of the healthy partners and siblings of the renal transplant recipients. We intend to include 10 healthy volunteers and 60 renal transplant recipients (20 on prednisolone and a CNI, 20 on prednisolone and MMF and 20 on prednisolone and an mTORi.

Intervention: Dukoral® (SBL Vaccines) will be administered orally at baseline (day 0) and at day 14.

Laboratory analysis: Serum, peripheral blood mononuclear cells (PBMCs) and saliva is collected before the first vaccination (day 0) and at day 21. IgA and IgG in serum- and saliva is measured using Enzyme Immunoassay (EIA). The number of PMBCs that secrete IgA- or IgG upon stimulation with cholera toxin is measured using B-cell Enzyme-Linked Immunospot (ELISPOT). The analysis is performed at Leiden University Medical Center.

Statistical analysis: No formal sample-size calculation was performed. The crude outcome estimates will be adjusted for variables that may influence the outcome (age, time after transplantation, past treatment for transplant rejection, current renal function, cumulative prednisolone dose, serum concentration (i.e. area under the curve) of CNI, MMF and mTORi.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

HEALTHY VOLUNTEERS

Inclusion criteria:

  • Above 18 years of age
  • Informed consent

Exclusion Criteria:

  • History of an auto-immune disease (SLE, ANCA associated vasculitis, Goodpasture, Henoch Schonlein, cryoglobulinemia, secondary vasculitis, polyarteritis nodosa and immunodeficiency disorders like IgA deficiency)
  • Chronic infection
  • Past vaccination with Dukoral or another cholera or ETEC vaccine
  • History of infection with Vibrio cholerae
  • Episode of diarrhoea in the 6 months prior to inclusion
  • Allergy to vaccine-specific components
  • History of a severe allergic reaction to any vaccine
  • Treatment with blood products in the 3 months prior to inclusion
  • Current pregnancy or breastfeeding
  • Premenopausal women not willing to use contraceptives during the first 60 days after vaccination
  • Use of any immunosuppressive drug

RENAL TRANSPLANT RECIPIENTS

Inclusion Criteria:

  • Above 18 years of age
  • Creatinin clearance ≥ 40 ml/min measured in the 6 months prior to inclusion
  • Stable renal function for 1 year prior to inclusion
  • Stable immunosuppressive regimen of a CNI, MMF or mTORi combined with prednisolone for at least 3 months prior to inclusion
  • Informed Consent

Exclusion Criteria:

  • History of an auto-immune disease (SLE, ANCA associated vasculitis, Goodpasture, Henoch Schonlein, cryoglobulinemia, secondary vasculitis, polyarteritis nodosa and immunodeficiency disorders like IgA deficiency)
  • Chronic infection
  • Treatment for rejection of the transplant in the past 1 year prior to inclusion
  • Past vaccination with Dukoral or another cholera or ETEC vaccine
  • History of infection with Vibrio cholerae
  • Episode of diarrhoea in the 6 months prior to inclusion
  • Allergy to vaccine-specific components
  • History of a severe allergic reaction to any vaccine
  • Treatment with blood products in the 3 months prior to inclusion
  • Current pregnancy or breastfeeding
  • Premenopausal women not willing to use contraceptives during the first 60 days after vaccination
  • Use of an immunosuppressive drug other than CNI, MMF, mTORi or prednisolone at the the time of inclusion
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01109914

Contacts
Contact: Darius Soonawala, MD +31-71-5265815 D.Soonawala@lumc.nl

Locations
Netherlands
Leiden Univeristy Medical Centre Recruiting
Leiden, Zuid-Holland, Netherlands, 2333 ZA
Contact: Darius Soonawala, MD     +31-71-5265815     D.Soonawala@lumc.nl    
Principal Investigator: Leo G Visser, MD, PhD            
Sponsors and Collaborators
Leiden University Medical Center
Crucell B.V., Leiden, the Netherlands
Investigators
Principal Investigator: Leo G Visser, MD PhD Leiden University Medical Center
Study Director: Darius Soonawala, MD Leiden University Medical Center
Study Chair: O W Bredewold, MD Leiden University Medical Center
Study Chair: J W de Fijter, Prof PhD Leiden University Medical Center
Study Chair: Marjolein AC Uijlings Leiden University Medical Center
Study Chair: Emile FF Jonker, MD Leiden University Medical Center
  More Information

No publications provided

Responsible Party: Darius Soonawala, Drs, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01109914     History of Changes
Other Study ID Numbers: MICH P10.011
Study First Received: April 22, 2010
Last Updated: August 1, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
Renal transplantation
Immunosuppression
ETEC
 Dukoral
Vaccination
Immunity, Humoral

ClinicalTrials.gov processed this record on May 19, 2013