Chronic Kidney DiseasePhase 1CLEAR-PLUSNCT03576716

Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation

A Phase 1 study testing D6-25-hydroxyvitamin D3 in people with Chronic Kidney Disease, run by University of Washington at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The goal of this study is to determine how 25(OH)D3 clearance is affected by vitamin D3 supplementation using a gold standard pharmacokinetic approach. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Kidney Disease
What is being tested?: D6-25-hydroxyvitamin D3
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 1 siteUnited States
Study dates: 1 Jun 2018to 1 Jan 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Successful prior completion of related protocol CLEAR (NCT02937350) or CLEAR-CF (NCT03104855)
Age ≥ 18 years
Self-reported race Caucasian, African American, or African

Who cannot join

Primary hyperparathyroidism
Gastric bypass
Tuberculosis or sarcoidosis
Current pregnancy
Child-Pugh Class B or C cirrhosis (i.e. cirrhosis with ascites, hepatic encephalopathy, bilirubin >=2 mg/dL, serum albumin <=3.5 g/dL, or PT >= 4 seconds)
History of kidney transplantation (unless failed transplant now treated with hemodialysis)

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Use of 1,25(OH)2D3 or an analogue, calcimimetics, or medications known to induce CYP24A1 within 4 weeks (wash-out allowed)
Serum calcium > 10.1 mg/dL
Hemoglobin < 10 g/dL

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Washington
Seattle, Washington, 98195

Other trials in United States

About this study

The goal of this study is to determine how 25(OH)D3 clearance is affected by vitamin D3 supplementation using a gold standard pharmacokinetic approach.

Read the detailed description

We expect that this study will enhance interpretation of available diagnostic tests, inform the results of ongoing large clinical trials of vitamin D supplements, and help develop new strategies to target vitamin D to improve health.

Conditions: Chronic Kidney Disease
Being tested: D6-25-hydroxyvitamin D3
Keywords: chronic kidney disease, vitamin d catabolism
Medical subject headings: Renal Insufficiency, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

D6-25-hydroxyvitamin D3Drug
Also called stable isotope deuterium-labeled 25(OH)D3
Intravenous administration of a deuterium-labeled 25(OH)D3 to evaluate the metabolic clearance of 25(OH)D3

Study groups in NCT03576716
Study group	Role	What they receive
Study Population	Experimental	D6-25-hydroxyvitamin D3 with vitamin D3 Receives: Drug: D6-25-hydroxyvitamin D3

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Metabolic Clearance of D6-25(OH)D3
Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method. Change in clearance of D6-25(OH)D3 will be calculated as D6-25(OH)D3 clearance measured during CLEAR-PLUS minus D6-25(OH)D3 clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.
Measured: Baseline, 6 months

Secondary outcomes (3)

Change in AUC of D6-25(OH)D3
AUC is calculated using the linear trapezoidal method. Change in the AUC of D6-25(OH)D3 will be calculated as D6-25(OH)D3 AUC measured during CLEAR-PLUS minus D6-25(OH)D3 AUC previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.
Measured: Baseline, 6 months
Change in Terminal Half-life of D6-25(OH)D3
Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations. Change in the terminal half-life of D6-25(OH)D3 will be calculated as D6-25(OH)D3 half-life measured during CLEAR-PLUS minus D6-25(OH)D3 half-life previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.
Measured: Baseline, 6 months
Change in Volume of Distribution of D6-25(OH)D3
Volume of distribution in the central compartment is calculated as dose/C0, where dose is the administered dose of 25(OH)D3 and C0 is the initial (estimated) concentration of drug in plasma. Change in the volume of distribution of D6-25(OH)D3 will be calculated as D6-25(OH)D3 volume of distribution measured during CLEAR-PLUS minus D6-25(OH)D3 volume of distribution previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.
Measured: Baseline, 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 20181 Jan 2021

First posted3 Jul 2018
Study start1 Jun 2018
Primary completion8 Jul 2019
Study completion1 Jan 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
More trials run by University of WashingtonThe 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 1
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03576716
Sponsor's protocol ID: STUDY00000608
Other IDs: R01DK099199
Acronym: CLEAR-PLUS
Status last verified: May 2022
First submitted: 22 Jun 2018
Last updated: 17 May 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Coded individual participant data may be shared with other researchers under mutually agreeable terms.

Publications

Hsu S, Zelnick LR, Lin YS, Best CM, Kestenbaum B, Thummel KE, Rose LM, Hoofnagle AN, de Boer IH. Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic Study. J Am Soc Nephrol. 2021 Jan;32(1):188-198. doi: 10.1681/ASN.2020050625. Epub 2020 Oct 28.
PubMed 33115916

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 17 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation
ClinicalTrials.gov ID: NCT03576716
Acronym / sponsor ID: CLEAR-PLUS / STUDY00000608
Conditions: Chronic Kidney Disease
Keywords: chronic kidney disease, vitamin d catabolism
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: University of WashingtonUniversity, hospital or other
Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study start: 1 Jun 2018 (actual)
Primary completion: 8 Jul 2019 (actual)
Study completion: 1 Jan 2021 (actual)
First posted: 3 Jul 2018 (actual)
Results: Posted 28 Sep 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The goal of this study is to determine how 25(OH)D3 clearance is affected by vitamin D3 supplementation using a gold standard pharmacokinetic approach.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Study Population	Experimental	Drug: D6-25-hydroxyvitamin D3D6-25-hydroxyvitamin D3 with vitamin D3

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Successful prior completion of related protocol CLEAR (NCT02937350) or CLEAR-CF (NCT03104855)
Age ≥ 18 years
Self-reported race Caucasian, African American, or African

Key exclusion criteria (9 listed)

Primary hyperparathyroidism
Gastric bypass
Tuberculosis or sarcoidosis
Current pregnancy
Child-Pugh Class B or C cirrhosis (i.e. cirrhosis with ascites, hepatic encephalopathy, bilirubin >=2 mg/dL, serum albumin <=3.5 g/dL, or PT >= 4 seconds)

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
D6-25-hydroxyvitamin D3Also: stable isotope deuterium-labeled 25(OH)D3Intravenous administration of a deuterium-labeled 25(OH)D3 to evaluate the metabolic clearance of 25(OH)D3	Drug	Study Population

Primary outcome

Change in Metabolic Clearance of D6-25(OH)D3
Time frame: Baseline, 6 months
Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method. Change in clearance of D6-25(OH)D3 will be calculated as D6-25(OH)D3 clearance measured during CLEAR-PLUS minus D6-25(OH)D3 clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

3 secondary outcomes

Change in AUC of D6-25(OH)D3
Time frame: Baseline, 6 months
Change in Terminal Half-life of D6-25(OH)D3
Time frame: Baseline, 6 months
Change in Volume of Distribution of D6-25(OH)D3
Time frame: Baseline, 6 months

Results and safety

Results posted to the registry on 28 Sep 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Healthy Controls	10	10
CKD Group	9	8

Primary outcome: Change in Metabolic Clearance of D6-25(OH)D3

Time frame: Baseline, 6 months. Mean (95% Confidence Interval). Unit: ml/d

Measure	Healthy Controls n = 10	CKD Group n = 8
Value	21 (-63 to 105)	5 (-45 to 55)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 8 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Participants	0 of 18 (0%)	6 of 18 (33.3%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33115916Hsu S, Zelnick LR, Lin YS, Best CM, Kestenbaum B, Thummel KE, Rose LM, Hoofnagle AN, de Boer IH. Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic Study. J Am Soc Nephrol. 2021 Jan;32(1):188-198. doi: 10.1681/ASN.2020050625. Epub 2020 Oct 28.
Individual participant dataSharing planned: No. Coded individual participant data may be shared with other researchers under mutually agreeable terms.

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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.

Ian de Boer, MD, MS principal investigator

University of Washington

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing D6-25-hydroxyvitamin D3 in people with Chronic Kidney Disease, run by University of Washington at 1 site 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 3 inclusion and 9 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 17 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Metabolic Clearance of D6-25(OH)D3 (time frame: Baseline, 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03576716, which also lists 1 linked publication.

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 17 May 2022.