Metabolic and Infectious Complications Post Belatacept Conversion

NCT05316038 | Unknown DMC

• 1 other identifier: Belaswitch_Grenoble
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

The BELASWITCH study is a prospective single-centre study including all kidney transplant patients for whom a conversion from Tacrolimus to Belatacept has been decided by the transplant clinicians of the Grenoble Alpes University Hospital. Each patient will be included at the time of conversion (patients stable on Tacrolimus for at least 6 months) and will be their own control 1 year after conversion to Belatacept. The study has two components:

• A "Metabolic" benefit arm: the investigators assume that conversion from Tacrolimus to Belatacept reduces the risk of diabetes by reducing the level of insulin resistance.
• An "Infectious" risk arm: measurement of the viral load of Torque Teno Virus to assess the state of immunosuppression of patients. In this sense, the investigators hypothesise that it could serve as a biomarker of immunodepression in this population.

Conditions

Kidney Transplant Infection; Cardiovascular Diseases; Immunosuppression; Kidney Transplant; Complications

Keywords

transplantation; Belatacept; TTV; Cardio-vascular complications

Outcome Measures

Primary Outcomes (2)

• Oral glucose tolerance test results in kidney transplant patients on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 1 year

  1 year

• Torque TenoVirus replication (in copies/ml) in kidney transplant patients on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year.

  1 year

Secondary Outcomes (14)

• Comparison of weight and height (combined to report BMI in kg/m^2) on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year

  1 year

• Comparison of blood pressure in mmHg on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year

  1 year

• Comparison of abdominal perimeter of kidney transplant recipients in centimeters on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year

  1 year

• Comparison of HbA1c measurment in percentage on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year

  1 year

• Comparison of LDL measurment in g/l on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year

  1 year

Study Arms (1)

Belatacept cohort

Kidney transplanted patients for whom a conversion from Tacrolimus to belatacept has been decided will be included in this cohort.

Diagnostic Test: Oral glucose tolerance test

Interventions

Oral glucose tolerance test DIAGNOSTIC_TEST

The test is performed on an empty stomach for at least 10 hours. The first blood sugar level is taken on an empty stomach. Then ingestion of 75g of sugar. A second blood test takes place 1 hour after the sugar intake and the third blood sugar test takes place 2 hours after the sugar intake.

Belatacept cohort

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The BELASWITCH study cohort is a prospective single-centre study including all adult kidney transplant recipients for whom a conversion from Tacrolimus to Belatacept has been decided by the transplant clinicians of the Grenoble Alpes University Hospital. Each patient will be included at the time of conversion (patients stable on Tacrolimus for at least 6 months) and will be their own control 1 year after conversion to Belatacept.

You may qualify if:

• Adult patients who have had a kidney transplant more than 6 months ago.
• Whose immunosuppression includes stable Tacrolimus (change in dose or dosage form allowed) for at least 3 months.
• Therapeutic plan to change Tacrolimus-based immunosuppression to Belatacept
• Having signed the consent of collection CRB04 - Nephrology Collection (last authorization number: AC-2019-3627) and the BELASWITCH protocol consent.

You may not qualify if:

• Subjects under guardianship or deprived of liberty
• Patients who object to the use of their data and/or samples in the research
• Patients having received an immunosuppressive treatment different from the standard one (Tacrolimus, mycophenolate mofetil or Everolimus, corticosteroids)
• ABO and/or HLA incompatible kidney transplantation

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Related Publications (19)

• Collins AJ, Foley RN, Gilbertson DT, Chen SC. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl (2011). 2015 Jun;5(1):2-7. doi: 10.1038/kisup.2015.2.

  PMID: 26097778 RESULT

• Dharnidharka VR. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005 Nov 10;353(19):2085-6; author reply 2085-6. doi: 10.1056/NEJM200511103531919. No abstract available.

  PMID: 16282187 RESULT

• Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, Moal MC, Mondragon-Ramirez GA, Kothari J, Polinsky MS, Meier-Kriesche HU, Munier S, Larsen CP. Belatacept and Long-Term Outcomes in Kidney Transplantation. N Engl J Med. 2016 Jan 28;374(4):333-43. doi: 10.1056/NEJMoa1506027.

  PMID: 26816011 RESULT

• Durrbach A, Pestana JM, Florman S, Del Carmen Rial M, Rostaing L, Kuypers D, Matas A, Wekerle T, Polinsky M, Meier-Kriesche HU, Munier S, Grinyo JM. Long-Term Outcomes in Belatacept- Versus Cyclosporine-Treated Recipients of Extended Criteria Donor Kidneys: Final Results From BENEFIT-EXT, a Phase III Randomized Study. Am J Transplant. 2016 Nov;16(11):3192-3201. doi: 10.1111/ajt.13830. Epub 2016 Jun 9.

  PMID: 27130868 RESULT

• Baron PW, Infante S, Peters R, Tilahun J, Weissman J, Delgado L, Kore AH, Beeson WL, de Vera ME. Post-Transplant Diabetes Mellitus After Kidney Transplant in Hispanics and Caucasians Treated with Tacrolimus-Based Immunosuppression. Ann Transplant. 2017 May 23;22:309-314. doi: 10.12659/aot.903079.

  PMID: 28533501 RESULT

• Iida S, Ishida H, Tokumoto T, Omoto K, Shirakawa H, Shimizu T, Amano H, Setoguchi K, Nozaki T, Toki D, Tokita D, Tanabe K. New-onset diabetes after transplantation in tacrolimus-treated, living kidney transplantation: long-term impact and utility of the pre-transplant OGTT. Int Urol Nephrol. 2010 Dec;42(4):935-45. doi: 10.1007/s11255-010-9712-0. Epub 2010 Feb 19.

  PMID: 20169408 RESULT

• Drachenberg CB, Klassen DK, Weir MR, Wiland A, Fink JC, Bartlett ST, Cangro CB, Blahut S, Papadimitriou JC. Islet cell damage associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation. Transplantation. 1999 Aug 15;68(3):396-402. doi: 10.1097/00007890-199908150-00012.

  PMID: 10459544 RESULT

• Terrec F, Jouve T, Naciri-Bennani H, Benhamou PY, Malvezzi P, Janbon B, Giovannini D, Rostaing L, Noble J. Late Conversion From Calcineurin Inhibitors to Belatacept in Kidney-Transplant Recipients Has a Significant Beneficial Impact on Glycemic Parameters. Transplant Direct. 2019 Dec 24;6(1):e517. doi: 10.1097/TXD.0000000000000964. eCollection 2020 Jan.

  PMID: 32047845 RESULT

• Rangaswami J, Mathew RO, Parasuraman R, Tantisattamo E, Lubetzky M, Rao S, Yaqub MS, Birdwell KA, Bennett W, Dalal P, Kapoor R, Lerma EV, Lerman M, McCormick N, Bangalore S, McCullough PA, Dadhania DM. Cardiovascular disease in the kidney transplant recipient: epidemiology, diagnosis and management strategies. Nephrol Dial Transplant. 2019 May 1;34(5):760-773. doi: 10.1093/ndt/gfz053.

  PMID: 30984976 RESULT

• Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD, Nordlander R, Maggioni A, Dickstein K, Zelenkofske S, Leimberger JD, Califf RM, Pfeffer MA. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004 Sep 23;351(13):1285-95. doi: 10.1056/NEJMoa041365.

  PMID: 15385655 RESULT

• Nankivell BJ, P'Ng CH, O'Connell PJ, Chapman JR. Calcineurin Inhibitor Nephrotoxicity Through the Lens of Longitudinal Histology: Comparison of Cyclosporine and Tacrolimus Eras. Transplantation. 2016 Aug;100(8):1723-31. doi: 10.1097/TP.0000000000001243.

  PMID: 27306529 RESULT

• Bertrand D, Terrec F, Etienne I, Chavarot N, Sberro R, Gatault P, Garrouste C, Bouvier N, Grall-Jezequel A, Jaureguy M, Caillard S, Thervet E, Colosio C, Golbin L, Rerolle JP, Thierry A, Sayegh J, Janbon B, Malvezzi P, Jouve T, Rostaing L, Noble J. Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort. J Clin Med. 2020 Oct 28;9(11):3479. doi: 10.3390/jcm9113479.

  PMID: 33126667 RESULT

• Everly MJ, Roberts M, Townsend R, Bray RA, Gebel HM. Comparison of de novo IgM and IgG anti-HLA DSAs between belatacept- and calcineurin-treated patients: An analysis of the BENEFIT and BENEFIT-EXT trial cohorts. Am J Transplant. 2018 Sep;18(9):2305-2313. doi: 10.1111/ajt.14939. Epub 2018 Jun 16.

  PMID: 29767445 RESULT

• Bertrand D, Chavarot N, Gatault P, Garrouste C, Bouvier N, Grall-Jezequel A, Jaureguy M, Caillard S, Lemoine M, Colosio C, Golbin L, Rerolle JP, Thierry A, Sayegh J, Etienne I, Lebourg L, Sberro R, Guerrot D. Opportunistic infections after conversion to belatacept in kidney transplantation. Nephrol Dial Transplant. 2020 Feb 1;35(2):336-345. doi: 10.1093/ndt/gfz255.

  PMID: 32030416 RESULT

• Noble J, Jouve T, Janbon B, Rostaing L, Malvezzi P. Belatacept in kidney transplantation and its limitations. Expert Rev Clin Immunol. 2019 Apr;15(4):359-367. doi: 10.1080/1744666X.2019.1574570. Epub 2019 Feb 7.

  PMID: 30676815 RESULT

• Noble J, Langello A, Bouchut W, Lupo J, Lombardo D, Rostaing L. Immune Response Post-SARS-CoV-2 mRNA Vaccination in Kidney Transplant Recipients Receiving Belatacept. Transplantation. 2021 Nov 1;105(11):e259-e260. doi: 10.1097/TP.0000000000003923. No abstract available.

  PMID: 34387243 RESULT

• Strassl R, Doberer K, Rasoul-Rockenschaub S, Herkner H, Gorzer I, Klager JP, Schmidt R, Haslacher H, Schiemann M, Eskandary FA, Kikic Z, Reindl-Schwaighofer R, Puchhammer-Stockl E, Bohmig GA, Bond G. Torque Teno Virus for Risk Stratification of Acute Biopsy-Proven Alloreactivity in Kidney Transplant Recipients. J Infect Dis. 2019 May 24;219(12):1934-1939. doi: 10.1093/infdis/jiz039.

  PMID: 30668796 RESULT

• Doberer K, Haupenthal F, Nackenhorst M, Bauernfeind F, Dermuth F, Eigenschink M, Schiemann M, Klager J, Gorzer I, Eskandary F, Reindl-Schwaighofer R, Kikic Z, Bohmig G, Strassl R, Regele H, Puchhammer-Stockl E, Bond G. Torque Teno Virus Load Is Associated With Subclinical Alloreactivity in Kidney Transplant Recipients: A Prospective Observational Trial. Transplantation. 2021 Sep 1;105(9):2112-2118. doi: 10.1097/TP.0000000000003619.

  PMID: 33587432 RESULT

• Sharts-Hopko NC. Hormone replacement therapy and cardiovascular health in midlife women. Medsurg Nurs. 1995 Aug;4(4):314-6. No abstract available.

  PMID: 7627237 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

peripheral blood mononucleated cell Plasma

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Glucose Tolerance Test

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Central Study Contacts

Johan Noble, M.D.

CONTACT

+33 4 76 76 74 73; jnoble@chu-grenoble.fr

Claire Bollart

CONTACT

+33 4 76 76 68 14; CBollart@chu-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pincipal investigator

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: April 7, 2022
• Study Start: June 1, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2024
• Last Updated: April 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share