Chronic Kidney DiseasesNCT02360644
Drug Metabolizing Enzyme and Transporter Function in Chronic Kidney Disease
A study testing Cholecalciferol in people with Chronic Kidney Diseases and Deficiency, Vitamin D, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
This study investigates the effect of vitamin D deficiency on drug metabolism and transport in patients with chronic kidney disease (CKD) and in healthy controls. The central hypothesis is that vitamin D concentrations independently affect metabolism and transport function in CKD patients. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Diseases, Deficiency, Vitamin D
- What is being tested?
- Cholecalciferol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2014to 1 Feb 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- vitamin D deficient (<30 ng/mL)
- hemoglobin >10 g/dL
- willing to abstain from fruit juices or alcohol within 7 days of PK assessments
- no changes in prescription or nonprescription medications within 4 wks of study start
- age 18-70 yrs
- If a diagnosis of CKD, must be due to diabetes mellitus or hypertension
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- Signed informed consent
- vitamin D deficient (<30 ng/mL)
- hemoglobin >10 g/dL
- willing to abstain from fruit juices or alcohol within 7 days of PK assessments
- no changes in prescription or nonprescription medications within 4 wks of study start
- age 18-70 yrs
- Signed informed consent
Who cannot join
- History of >14 alcoholic drinks/wk
- Not likely to be compliant with study visits
- Pregnant or lactating
- Predisposition to or history of hypercalcemia
- History of allergy, sensitivity, or contraindication to probe drugs (seizures, drug metabolism interactions, etc)
- Use of prescribed or nonprescribed therapies that could interact with probe drugs (including prototypical inhibitors or inducers)
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- Active autoimmune disease or active/recent infections requiring antimicrobial treatment within the previous 4 wks will be excluded to minimize inflammatory-mediated changes in vitamin D status and patient heterogeneity.
- Presence of clinically significant hepatic insufficiency (total bilirubin greater than 1.5 times the upper limit of normal or transaminase (ALT, AST) elevations greater than 2 times the upper limit of the laboratory reference range or liver disease
- Active seizure disorder or those patients receiving large doses of medications that are known to reduce seizure threshold
- Currently receiving cholecalciferol or a vitamin D analogue
- History of >14 alcoholic drinks/wk
- Not likely to be compliant with study visits
- Pregnant or lactating
- Predisposition to or history of hypercalcemia
- History of allergy, sensitivity, or contraindication to probe drugs (seizures, drug metabolism interactions, etc)
- Use of prescribed or nonprescribed therapies that could interact with probe drugs (including prototypical inhibitors or inducers)
- Active autoimmune disease or active/recent infections requiring antimicrobial treatment within the previous 4 wks will be excluded to minimize inflammatory-mediated changes in vitamin D status and patient heterogeneity.
- Presence of clinically significant hepatic insufficiency (total bilirubin greater than 1.5 times the upper limit of normal or transaminase (ALT, AST) elevations greater than 2 times the upper limit of the laboratory reference range or liver disease
- Active seizure disorder or those patients receiving large doses of medications that are known to reduce seizure threshold
- Currently receiving cholecalciferol or a vitamin D analogue
- Any clinical evidence of chronic kidney disease as defined by the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF DOQI) guidelines
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Colorado
Aurora, Colorado, 80045
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
About this study
This study investigates the effect of vitamin D deficiency on drug metabolism and transport in patients with chronic kidney disease (CKD) and in healthy controls.
The central hypothesis is that vitamin D concentrations independently affect metabolism and transport function in CKD patients. An over-arching goal of this proposal is to make drug therapies safer and more effective to reduce the significant morbidity and mortality in patients with CKD.
Read the detailed description
Specific Aim 1: Determine the effect of vitamin D deficiency and repletion on xenobiotic clearance in vivo. The study will mechanistically evaluate the function of major pathways of metabolism and transport by prospectively studying clearance phenotypes utilizing "probe" drugs commonly used for this purpose in CKD patients and healthy volunteers under vitamin D deficient and replete states. Bupropion, midazolam, olmesartan, fexofenadine, in addition to an endogenous probe (N-methylnicotinamide), will be used to phenotype major phase I drug metabolizing enzymes [cytochrome P450 2B6 (CYP2B6), cytochrome P450 3A4/5 (CYP3A4/5)], and transporters [multidrug resistance associated protein 2 (MRP2), P-glycoprotein (P-gp), and multidrug and toxin extrusion protein 1/2K (MATE1/2K)], respectively. Hypothesis: The in vivo function of individual pathways of xenobiotic metabolism and transport are affected by vitamin D status (and CKD).
Specific Aim 2: Determine the effect of CKD on the in vivo function of individual CYPs responsible for vitamin D metabolism and the pharmacokinetics of cholecalciferol (vitamin D3). The research will prospectively measure the activity of CYP450s responsible for cholecalciferol metabolism, and simultaneously evaluate the pharmacokinetics (PK) of cholecalciferol after single- and multiple-dose administration to CKD patients (stages 1-5) and healthy volunteers. Hypothesis: CKD alters the activity of individual CYPs responsible for vitamin D metabolism, leading to modified clearance of cholecalciferol.
- Conditions
- Chronic Kidney Diseases, Deficiency, Vitamin D
- Being tested
- Cholecalciferol
- Medical subject headings
- Renal Insufficiency, Chronic, Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CholecalciferolDietary supplement
Also called Vitamin D
Vitamin D deficient patients, in both Arms, will be administered Cholecalciferol 5,000 IU daily.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Drug Metabolism and Transport | Experimental | The aim of Arm 1 is to determine the effect of vitamin D deficiency and repletion on xenobiotic clearance in vivo. The study will evaluate the in vivo function of targeted metabolism and transport pathways in 40 CKD and 18 healthy volunteer subjects (controls) under the influence of a vitamin D depleted state and repeated under a vitamin D replete state with cholecalciferol.
The function of two major phase I drug metabolizing enzymes (CYP2B6, CYP3A), and three transporters [P-gp, MRP2, and MATE1/2K] will be assessed by administering oral bupropion, midazolam, olmesartan, and fexofenadine. Receives: Dietary Supplement: Cholecalciferol |
| Arm 2: Vitamin D Pharmacokinetics | Experimental | The aim of Arm 2 is to determine the effect of CKD on the in vivo function of individual CYP450s responsible for vitamin D metabolism and their functional relevance on the pharmacokinetics of cholecalciferol. A total of 90 CKD subjects will be enrolled [30 per group: group I (CKD stage 1/2), group II (CKD stage 3), and group III (CKD stage 4/5, pre-ESRD)], as well as 30 healthy controls. Receives: Dietary Supplement: Cholecalciferol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in area under the plasma concentration time curves for probe drugs (bupropion, midazolam, olmesartan and fexofenadine) from baseline to 12 weeks.
Change in area under the plasma concentration time curves for probe drugs (bupropion, midazolam, olmesartan, and fexofenadine) at 12 weeks.
Measured: 12 weeks
Secondary outcomes (1)
Change in area under the plasma concentration time curves for cholecalciferol from baseline to 12 weeks.
Change in area under the plasma concentration time curves for cholecalciferol at 12 weeks.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2015 (estimated)
- Study startOct 2014
- Primary completion1 Feb 2019
- Study completion1 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseasesStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh, National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Sponsor
- Investigators
- Melanie Joy, PharmD, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02360644
- Sponsor's protocol ID
- 14-1150
- Other IDs
- UL1TR001082, 1R01GM107122-01A1
- Status last verified
- Jun 2021
- First submitted
- 19 Dec 2014
- Last updated
- 30 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug Metabolizing Enzyme and Transporter Function in Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT02360644
- Acronym / sponsor ID
- 14-1150
- Conditions
- Chronic Kidney Diseases, Deficiency, Vitamin D
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- University of Pittsburgh, National Institute of General Medical Sciences (NIGMS)
- Study start
- Oct 2014
- Primary completion
- 1 Feb 2019 (actual)
- Study completion
- 1 Feb 2019 (actual)
- First posted
- 10 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study investigates the effect of vitamin D deficiency on drug metabolism and transport in patients with chronic kidney disease (CKD) and in healthy controls.
The central hypothesis is that vitamin D concentrations independently affect metabolism and transport function in CKD patients. An over-arching goal of this proposal is to make drug therapies safer and more effective to reduce the significant morbidity and mortality in patients with CKD.
Detailed description
Specific Aim 1: Determine the effect of vitamin D deficiency and repletion on xenobiotic clearance in vivo. The study will mechanistically evaluate the function of major pathways of metabolism and transport by prospectively studying clearance phenotypes utilizing "probe" drugs commonly used for this purpose in CKD patients and healthy volunteers under vitamin D deficient and replete states. Bupropion, midazolam, olmesartan, fexofenadine, in addition to an endogenous probe (N-methylnicotinamide), will be used to phenotype major phase I drug metabolizing enzymes [cytochrome P450 2B6 (CYP2B6), cytochrome P450 3A4/5 (CYP3A4/5)], and transporters [multidrug resistance associated protein 2 (MRP2), P-glycoprotein (P-gp), and multidrug and toxin extrusion protein 1/2K (MATE1/2K)], respectively. Hypothesis: The in vivo function of individual pathways of xenobiotic metabolism and transport are affected by vitamin D status (and CKD).
Specific Aim 2: Determine the effect of CKD on the in vivo function of individual CYPs responsible for vitamin D metabolism and the pharmacokinetics of cholecalciferol (vitamin D3). The research will prospectively measure the activity of CYP450s responsible for cholecalciferol metabolism, and simultaneously evaluate the pharmacokinetics (PK) of cholecalciferol after single- and multiple-dose administration to CKD patients (stages 1-5) and healthy volunteers. Hypothesis: CKD alters the activity of individual CYPs responsible for vitamin D metabolism, leading to modified clearance of cholecalciferol.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Drug Metabolism and Transport | Experimental | Dietary Supplement: CholecalciferolThe aim of Arm 1 is to determine the effect of vitamin D deficiency and repletion on xenobiotic clearance in vivo. The study will evaluate the in vivo function of targeted metabolism and transport pathways in 40 CKD and 18 healthy volunteer subjects (controls) under the influence of a vitamin D depleted state and repeated under a vitamin D replete state with cholecalciferol. The function of two major phase I drug metabolizing enzymes (CYP2B6, CYP3A), and three transporters [P-gp, MRP2, and MATE1/2K] will be assessed by administering oral bupropion, midazolam, olmesartan, and fexofenadine. |
| Arm 2: Vitamin D Pharmacokinetics | Experimental | Dietary Supplement: CholecalciferolThe aim of Arm 2 is to determine the effect of CKD on the in vivo function of individual CYP450s responsible for vitamin D metabolism and their functional relevance on the pharmacokinetics of cholecalciferol. A total of 90 CKD subjects will be enrolled [30 per group: group I (CKD stage 1/2), group II (CKD stage 3), and group III (CKD stage 4/5, pre-ESRD)], as well as 30 healthy controls. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- vitamin D deficient (<30 ng/mL)
- hemoglobin >10 g/dL
- willing to abstain from fruit juices or alcohol within 7 days of PK assessments
- no changes in prescription or nonprescription medications within 4 wks of study start
- age 18-70 yrs
Key exclusion criteria (21 listed)
- History of >14 alcoholic drinks/wk
- Not likely to be compliant with study visits
- Pregnant or lactating
- Predisposition to or history of hypercalcemia
- History of allergy, sensitivity, or contraindication to probe drugs (seizures, drug metabolism interactions, etc)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CholecalciferolAlso: Vitamin DVitamin D deficient patients, in both Arms, will be administered Cholecalciferol 5,000 IU daily. | Dietary supplement | Arm 1: Drug Metabolism and Transport, Arm 2: Vitamin D Pharmacokinetics |
Primary outcome
Change in area under the plasma concentration time curves for probe drugs (bupropion, midazolam, olmesartan and fexofenadine) from baseline to 12 weeks.
Time frame: 12 weeks
Change in area under the plasma concentration time curves for probe drugs (bupropion, midazolam, olmesartan, and fexofenadine) at 12 weeks.
1 secondary outcome
Change in area under the plasma concentration time curves for cholecalciferol from baseline to 12 weeks.
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melanie Joy, PharmD, PhD principal investigator
University of Colorado, Denver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cholecalciferol in people with Chronic Kidney Diseases and Deficiency, Vitamin D, run by University of Colorado, Denver at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in area under the plasma concentration time curves for probe drugs (bupropion, midazolam, olmesartan and fexofenadine) from baseline to 12 weeks. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2021.