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Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients (COLCHINCAL)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01160276
First Posted: July 12, 2010
Last Update Posted: April 11, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
July 9, 2010
July 12, 2010
April 11, 2013
May 2010
January 2012   (Final data collection date for primary outcome measure)
Area under the curve of plasma concentration of colchicine over time 0-∞ [ Time Frame: 4 weeks ]
Same as current
Complete list of historical versions of study NCT01160276 on ClinicalTrials.gov Archive Site
  • Half-life of colchicine (T1/2). [ Time Frame: 4 weeks ]
  • AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp) [ Time Frame: 4 weeks ]
  • Cmax observed colchicine. [ Time Frame: 4 weeks ]
  • Residual tacrolimus or cyclosporine concentrations [ Time Frame: 4 weeks ]
  • ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group. [ Time Frame: 4 weeks ]
  • ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T. [ Time Frame: 4 weeks ]
  • CYP3A5 Genotype: search for the allele * 1 (rs 776746): 3 possible genotypes CYP3A5 * 3 / * 3 - CYP3A5 * 3 / * 1 - CYP3A5 * 1 / * 1. [ Time Frame: 4 weeks ]
  • GFR calculated by MDRD formula. [ Time Frame: 4 weeks ]
  • BMI [ Time Frame: 4 weeks ]
  • Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII) [ Time Frame: 4 weeks ]
Same as current
Not Provided
Not Provided
 
Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients
An Open Non Randomized Comparative Study Exploring Drug Interaction Between Colchicine and Calcineurin Inhibitors in 2 Groups (Ciclosporin Group and Tacrolimus Group) of Renal Graft Recipients

Ciclosporin inhibits P-glycoprotein should increase colchicine bioavailability whereas tacrolimus should not influence colchicine disposition.

This is a prospective, controlled, open labeled study performed in renal graft recipients comparing colchicine single dose (1mg) pharmacokinetics in 14 patients treated with tacrolimus and 14 patients treated with cyclosporin.

  • Renal transplantation >= one year
  • eGFR (MDRD) > 30ml/min
  • hemoglobin >= 11g/dl
  • treatment with tacrolimus or cyclosporine
  • no previous muscular disease
  • no drugs interfering with P-glycoprotein or CYP3A activity or expression outcomes
  • colchicine AUC, Cmax, T1/2
  • ABCB1C3435T, CYP3A5 and SLCO1B1 genotypes
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Renal Replacement Therapies
  • Drug: cyclosporine+colchicine
    the 14 patients of the 1st group are under cyclosporine and One pill of colchimax 1mg will be taken by all the patients at Day 3.
    Other Names:
    • Colchicine
    • Colchimax
  • Drug: tacrolimus
    the 14 patients of the second group are under tacrolimus and One pill of colchimax 1mg will be taken by all the patients at Day 3.
    Other Names:
    • Colchicine
    • Colchimax
  • Active Comparator: Cyclosporine
    The first group is composed of 14 renal graft recipients under cyclosporine
    Intervention: Drug: cyclosporine+colchicine
  • Active Comparator: Tacrolimus
    The second group is composed of 14 renal graft recipients under tacrolimus
    Intervention: Drug: tacrolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
17
January 2012
January 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with renal graft since at least 1 year
  • Patients treated with ciclosporin or tacrolimus
  • Are at least 18 years old.
  • Glomerular filtration rate above 30 ml / min calculated using the MDRD formula
  • Among the 14 patients receiving ciclosporin:
  • The genotype is not a criterion for inclusion
  • Among the 14 patients with tacrolimus treatment:
  • 7 genotype ABCB1 3435CC, 7 genotype ABCB1 3435TT
  • Recent (1 month) residual concentration of tacrolimus between 5-10ng/ml
  • Recent (1 month) residual concentration of ciclosporin between 100-200ng/ml
  • For women : a negative pregnancy test (serum beta hCG)
  • Realization of a medical examination.
  • Informed consent and writing form.

Exclusion Criteria:

  • Abnormal transaminases (AST and ALT above the ULN Laboratory).
  • Underlying Liver Disease (steatosis, cirrhosis, chronic hepatitis, the virus of hepatitis C or B).
  • Previous history of muscle disease (drug related especially the statin type).
  • Leukopenia (WBC <3000/mm3).
  • Hemoglobin <11g/dl.
  • Patient treated by erythropoetin (whatever its hemoglobin value).
  • Abnormal CPK (greater than the ULN Laboratory).
  • Prior intolerance to colchicine.
  • Regular intake of the following medications associated with rhabdomyolyses: antipsychotics, cholesterol lowering agents (statins or fibrates), zidovudine, antidepressants (selective inhibitor of serotonin reuptake) and lithium.
  • Patient (e) can not refrain from consuming grapefruit juice.
  • Patient (e) taking a tea based on St John's wort.
  • Taking drugs inducers of P-gp or CYP3A4 (rifabutin, rifampin, carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, protease inhibitors, griseofulvin).
  • Taking drugs inhibitors of P-gp or CYP3A4 (quinidine, macrolide antibiotics, azole antifungals, protease inhibitors, amiodarone, diltiazem, verapamil).
  • Chronic diarrhea.
  • ABCB1 Genotype 3435CT for patients in the tacrolimus group.
  • Participation in another concurrent trial.
  • Patient (e) exclusion period of another trial.
  • Patient (e) having reached the maximum annual amount of compensation provided by law.
  • No affiliation to French social security scheme or without CMU.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
France
 
 
NCT01160276
P081105
Yes
Not Provided
Not Provided
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator: Antoine Jacquet, MD Nephrology Department of BICETRE Hospital
Assistance Publique - Hôpitaux de Paris
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP