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Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients (COLCHINCAL)
This study has been completed.
Sponsor:
Assistance Publique - Hôpitaux de Paris
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01160276
First received: July 9, 2010
Last updated: April 10, 2013
Last verified: April 2013
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Purpose
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 | Intervention | Phase |
|---|---|---|
| Renal Replacement Therapies | Drug: cyclosporine+colchicine Drug: tacrolimus | Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: 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 |
Resource links provided by NLM:
Further study details as provided by Assistance Publique - Hôpitaux de Paris:
Primary Outcome Measures:
- Area under the curve of plasma concentration of colchicine over time 0-∞ [ Time Frame: 4 weeks ]
Secondary Outcome Measures:
- 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 ]
| Enrollment: | 17 |
| Study Start Date: | May 2010 |
| Study Completion Date: | January 2012 |
| Primary Completion Date: | January 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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:
|
|
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:
|
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
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01160276
Please refer to this study by its ClinicalTrials.gov identifier: NCT01160276
Locations
| 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
| Principal Investigator: | Antoine Jacquet, MD | Nephrology Department of BICETRE Hospital |
More Information
| Responsible Party: | Assistance Publique - Hôpitaux de Paris |
| ClinicalTrials.gov Identifier: | NCT01160276 History of Changes |
| Other Study ID Numbers: |
P081105 |
| Study First Received: | July 9, 2010 |
| Last Updated: | April 10, 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:
|
Tacrolimus Cyclosporins Cyclosporine Calcineurin Inhibitors Colchicine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs 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 |
ClinicalTrials.gov processed this record on July 25, 2017