Metabolic and Infectious Complications Post Belatacept Conversion

Cardiovascular Diseases Clinical Trial

— Belaswitch  

Official title:

Study of the Impact of Belatacept Conversion on Metabolic and Infectious Complications in Kidney Transplant Recipients at Grenoble-Alpes University Hospital

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05316038
• Other study ID #: Belaswitch_Grenoble
• Status: Not yet recruiting
• Start date: June 1, 2022
• Est. completion date: June 1, 2024

Study information

• Verified date: March 2022
• Source: University Hospital, Grenoble
• Contact: Johan Noble, M.D.
• Phone: +33 4 76 76 74 73
• Email: jnoble[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2023
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

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

Intervention

Diagnostic Test:
• Oral glucose tolerance 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

References & Publications (19)

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 — View Citation

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 Ma — View Citation

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 b — View Citation

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. Opport — View Citation

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. — View Citation

Dharnidharka VR. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005 Nov 10;353(19):2085-6; author reply 2085-6. — View Citation

Doberer K, Haupenthal F, Nackenhorst M, Bauernfeind F, Dermuth F, Eigenschink M, Schiemann M, Kläger J, Görzer I, Eskandary F, Reindl-Schwaighofer R, Kikic Ž, Böhmig G, Strassl R, Regele H, Puchhammer-Stöckl E, Bond G. Torque Teno Virus Load Is Associated — View Citation

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. Tran — View Citation

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, Grinyó JM. Long-Term Outcomes in Belatacept- Versus Cyclosporine-Treated Recipients of Extended Criteria Donor Kidney — View Citation

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. — View Citation

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 p — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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 recip — View Citation

Sharts-Hopko NC. Hormone replacement therapy and cardiovascular health in midlife women. Medsurg Nurs. 1995 Aug;4(4):314-6. — View Citation

Strassl R, Doberer K, Rasoul-Rockenschaub S, Herkner H, Görzer I, Kläger JP, Schmidt R, Haslacher H, Schiemann M, Eskandary FA, Kikic Ž, Reindl-Schwaighofer R, Puchhammer-Stöckl E, Böhmig GA, Bond G. Torque Teno Virus for Risk Stratification of Acute Biop — View Citation

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 — View Citation

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):33 — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Comparison of HDL 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
Secondary	Comparison of triglycerides 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
Secondary	Number of major cardiovascular events (stroke, coronary syndrome, hospitalization for cardiac decompensation, death from cardiovascular causes)		1 year
Secondary	Correlation of TorqueTenoVirus replication in copies/ml with the occurrence of opportunistic infections (Cytomegalovirus, Epstein-Barr virus, BKVirus).	Opportunistic infections are defined as positive DNAemia in copies/ml	1 year
Secondary	Correlatation of TorqueTenoVirus replication (in copies/ml) with immunosuppressant assays: Tacrolimus (µg/l) at M-1 and D0 and Belatacept (µg/l) at M3, M6 and M12		1 year
Secondary	Correlation of TorqueTenoVirus in copies/ml and the risk of biopsy-proven renal transplant rejection up to M12 after conversion to Belatacept.	Rejection are defined according to the more recent histological Banff classification	1 year
Secondary	Compare the performance of TorqueTenoVirus quantitative polymerase chain reaction in copies/ml performed on plasma and whole blood samples		3 months
Secondary	Trough Plasma Concentration of Belatacept		3 months
Secondary	Area under the plasma concentration versus time curve (AUC) of Belatacept		3 months