Pharmacokinetics of Immunosuppressants in Renal Transplant Candidates Who Have Undergone Laparoscopic Sleeve Gastrectomy
Condition: End Stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate how quickly and to what extent different
      immunosuppressants are absorbed into the blood (this is called pharmacokinetics) in renal
      transplant candidates who have undergone a laparoscopic sleeve gastrectomy. The immune system
      is the body's defense against diseases. It also attacks "foreign" tissues such as a
      transplanted kidney. Immunosuppressant medications such as Astagraf sustained release (XL),
      Prograf, and mycophenolate mofetil may be given to suppress the immune system following
      kidney transplantation and prevent rejection of a transplanted kidney. This study is being
      performed to determine if patients who undergo laparoscopic sleeve gastrectomy need different
      doses of immunosuppressant medications.
    

Detailed description: 
      Investigators propose a single dose, cross over pharmacokinetic study of Astagraf XL and
      Prograf® in combination with MMF in RTx candidates that have undergone LSG. Subjects at least
      three months post LSG and pre-renal transplant will undergo preliminary screening. The study
      population will consist of 24 male and female subjects, ≥ 18 years old from UC Health
      University Hospital and The Christ Hospital who meet the inclusion/exclusion criteria.

      Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf
      XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A
      full 24 hour PK profile will be constructed. After at least a one week washout period, the
      patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or
      Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated. The
      immunosuppressants chosen reflect the regimen most commonly prescribed to transplant
      recipients.

      Subjects participating in the study will have pharmacokinetic blood samples drawn over a 24
      hour time period in order to determine the AUC, Tmax, Cmax, and half-life of tacrolimus, MMF
      and their metabolites. Samples would be drawn prior to dosing (C0) and at 1, 1.5, 2, 2.5, 3,
      4, 6, 8, 12, 12.5, 13, 14, 15, 16, 18, 20 and 24 hours post dosing (18 time points) by
      venipuncture or IV.

      This study proposal represents a simple and expeditious method to achieve PK information in
      patients that have undergone LSG. If desired, study could be expanded to evaluate PK in
      additional patient groups such as pre and post LSG and/or pre and post renal transplant. The
      exact sample collection time will be recorded in the case report form. All deviations from
      the scheduled sampling time of more than 5 minutes for the first 4 hours after the AM dose
      (predose-4 hr) and first 4 hours of the PM dose (12 hr-16 hr), and more than 10 minutes for
      all remaining samples (6 hr-8 hr; 18 hr-24 hr) will be reported as a protocol deviation.
    

Intervention name(s): Astagraf XL; Prograf; Mycophenolate mofetil
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.; Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.; Two PK profiles will be obtained in each subject. Each subject will receive either Astagraf XL 8mg daily or Prograf® 4mg every 12 hours in combination with MMF 1000mg every 12 hours. A full 24 hour PK profile will be constructed. After at least a one week washout period, the patient will be crossed over to the alternative tacrolimus formulation (Astagraf XL or Prograf®) in combination with MMF 1000mg every 12 hours and the PK profile repeated.
Other intervention name(s): Tacrolimus sustained release; Tacrolimus; Cellcept
Intervention MeSH terms: Mycophenolic Acid; Tacrolimus
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Keywords: End stage renal disease; Renal transplant candidate; Laparoscopic sleeve gastrectomy; Immunosuppressants