Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT01160276
Recruitment Status : Completed
First Posted : July 12, 2010
Last Update Posted : April 11, 2013
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Renal Replacement Therapies Drug: cyclosporine+colchicine Drug: tacrolimus Phase 1

Detailed Description:
  • 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
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2010
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Cyclosporine
The first group is composed of 14 renal graft recipients under cyclosporine
 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
Active Comparator: Tacrolimus
The second group is composed of 14 renal graft recipients under tacrolimus
 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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Area under the curve of plasma concentration of colchicine over time 0-∞ [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. Half-life of colchicine (T1/2). [ Time Frame: 4 weeks ]
  2. AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp) [ Time Frame: 4 weeks ]
  3. Cmax observed colchicine. [ Time Frame: 4 weeks ]
  4. Residual tacrolimus or cyclosporine concentrations [ Time Frame: 4 weeks ]
  5. ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group. [ Time Frame: 4 weeks ]
  6. ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T. [ Time Frame: 4 weeks ]
  7. 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 ]
  8. GFR calculated by MDRD formula. [ Time Frame: 4 weeks ]
  9. BMI [ Time Frame: 4 weeks ]
  10. Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII) [ Time Frame: 4 weeks ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01160276


Locations
Layout table for location information
France
Assistance publique - Hôpitaux de Paris : Bicêtre Hospital
Le Kremlin Bicêtre, France, 94275
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Layout table for investigator information
Principal Investigator: Antoine Jacquet, MD Nephrology Department of BICETRE Hospital
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01160276    
Other Study ID Numbers: P081105
First Posted: July 12, 2010    Key Record Dates
Last Update Posted: April 11, 2013
Last Verified: April 2013
Keywords provided by Assistance Publique - Hôpitaux de Paris:
renal graft
colchicine
drug interaction
cyclosporine
tacrolimus
 renal transplantation
renal transplant
ABCB1
CYP3A5
SLCO1B1
Additional relevant MeSH terms:
Layout table for MeSH terms
Cyclosporine
Colchicine
Tacrolimus
Cyclosporins
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Gout Suppressants
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents