HealthyPhase 1NCT03136705
Healthy Combine Study
A Phase 1 study testing Nicotinamide and Lanthanum Carbonate in people with Healthy, run by Northwestern University at 1 site in United States.
Trial summary
STUDY SUMMARY Title: EFFECTS OF NICOTINAMIDE AND LANTHANUM CARBONATE ON PHOSPHORUS HOMEOSTASIS Protocol Number:STU00090161 Phase: Phase 1, detailed physiologic study Methodology: double blind, randomized, placebo-controlled, 2x2 factorial Study Duration: 12-18 months (to complete the entire study protocol) Study… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Nicotinamide and Lanthanum Carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Feb 2016to 1 Dec 2017
- 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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers
- Age ≥ 18 years, at the time of screening
- Normal renal function at screening, as defined by
- eGFR > 60
- no albuminuria
- normal urinalysis
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- normotensive, defined as blood pressure <140/85mmHg
- no known history of CKD
- Adequate organ and marrow function at screening as defined below:
- HCT ≥ 30%
- platelets ≥ 125,000/mm3
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit
- 25-hydroxyvitamin D ≥ 10mg/dL
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
- Ability to understand and the willingness to sign a written informed consent.
Who cannot join
- History of allergic reaction to nicotinamide, niacin (excluding flushing), and/or multivitamin preparations
- Liver disease, defined as known cirrhosis by imaging or physician diagnosis.
- Documented alcohol use > 14 drinks/week
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and/or alkaline phosphatase concentrations > 2 times the upper limit of the local laboratory reference range and/or total bilirubin concentration not within institutional limits.
- Creatine kinase (CK) concentrations > 2 times the upper limit of the local laboratory reference range at screening
- Major hemorrhagic event within the past six months from screening requiring inpatient admission.
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- Blood or platelet transfusion within the past six months from screening
- History of primary hyperparathyroidism
- Current, clinically significant malabsorption
- Anemia (screening HCT < 30%) at screening
- Plasma albumin < 2.5 mg/dl at screening
- 25-hydroxyvitamin D <10mg/dL at screening
- Inability or unwillingness to provide consent
- Current or recent treatment (within the last 14 days from screening) with niacin/nicotinamide > 100 mg/day
- Current or recent use of MVI containing niacin/nicotinamide > 100 mg/day
- Current use of Tums (or calcium carbonate taken for indigestion) at a dose of >1000 mg daily
- Current participation in another clinical trial or other interventional research
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Translational Metabolism and Health (CTMH), Northwestern University
Chicago, Illinois, 60611
About this study
Official title: Short-Term Effects of Nicotinamide and Lanthanum Carbonate on Phosphorus Homeostasis in Healthy Volunteers
STUDY SUMMARY Title: EFFECTS OF NICOTINAMIDE AND LANTHANUM CARBONATE ON PHOSPHORUS HOMEOSTASIS Protocol Number:STU00090161 Phase: Phase 1, detailed physiologic study Methodology: double blind, randomized, placebo-controlled, 2x2 factorial Study Duration: 12-18 months (to complete the entire study protocol) Study Center: Single-center Objectives: Define short-term effects of the interventions (lanthanum carbonate and nicotinamide) on indices of phosphate handling Number of Subjects: 80 Diagnosis and Main Inclusion Criteria: Healthy volunteers Study Product(s), Dose,Route, Regimen: Nicotinamide, 750 mg by mouth twice daily, Lanthanum carbonate, Fosrenol, 1000 mg by mouth three times daily with meals Duration of administration: 2 weeks (length of time study participants are enrolled in study) Reference therapy: reference is a placebo Statistical Methodology: Repeated measures analysis using mixed linear models
Read the detailed description
Chronic kidney disease (CKD) is a growing public health problem that increases risks of endstage renal disease (ESRD), cardiovascular disease (CVD), fractures, and death, and it poses an enormous financial burden on the US health system. Existing therapies modestly impact outcomes. Novel strategies targeting CKD-specific mechanisms are urgently needed to improve health and reduce cost.
CKD is complicated by disordered mineral metabolism, characterized by abnormal calcium and phosphate homeostasis, calcitriol and klotho deficiency, and elevated levels of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Elevated FGF23 is the earliest and most common manifestation of disordered mineral metabolism. Observational studies report independent associations between elevated phosphate and FGF23 blood levels and increased risks of ESRD, CVD and death. As potential explanatory mechanisms, phosphate excess induces arterial stiffness due to vascular calcification, and FGF23 excess contributes directly to the pathogenesis of left ventricular hypertrophy (LVH). Together, these effects promote CVD events and death.
Dietary phosphate absorption is a modifiable determinant of phosphate and FGF23 levels. Small studies of short duration suggest that phosphate binders and dietary phosphate modification in CKD can lower phosphate and FGF23 blood levels by reducing paracellular absorption of phosphate in the gut. However, animal studies demonstrate that compensatory upregulation of transcellular phosphate absorption via the sodium phosphate co-transporter, NPT2b, reduces the efficacy of these approaches. Since nicotinamide lowers plasma phosphate by reducing gut expression of NPT2b,the investigators hypothesize that use of nicotinamide combined with phosphate binders on a background of dietary phosphate moderation will most effectively reduce phosphate and FGF23 blood levels in CKD. The investigators plan to advance this approach in future randomized clinical trials.
The objective of this study is to perform a detailed physiologic study of healthy volunteers to assess the short-term effects of nicotinamide alone, lanthanum carbonate alone, or both in combination, on phosphate homeostasis. The results from healthy volunteers will provide information needed for optimal design of studies for patients with CKD.
- Conditions
- Healthy
- Being tested
- Nicotinamide, Lanthanum Carbonate, Lanthanum Carbonate Placebo, Nicotinamide Placebo
- Keywords
- Phosphorus Homeostasis, FGF23, Vitamin D
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicotinamideDrug
Nicotinamide tablet
Lanthanum CarbonateDrug
Also called Fosrenol
Lanthanum Carbonate tablet
Lanthanum Carbonate PlaceboDrug
Also called Placebo (for Lanthanum Carbonate 500mg tablet)
Sugar pill manufactured to look like Lanthanum Carbonate tablet
Nicotinamide PlaceboDrug
Also called Placebo (for Nicotinamide 750mg tablet)
Sugar pill manufactured to look like Nicotinamide tablet
| Study group | Role | What they receive |
|---|---|---|
| Lanthanum + Nicotinamide | Active comparator | Lanthanum Carbonate 1000mg orally three times daily with meals for 2 weeks and Nicotinamide 750mg orally twice daily for 2 weeks Receives: Drug: Nicotinamide; Drug: Lanthanum Carbonate |
| Lanthanum + Nicotinamide Placebo | Active comparator | Lanthanum Carbonate 1000mg orally three times daily with meals for 2 weeks and Nicotinamide Placebo orally twice daily for 2 weeks Receives: Drug: Lanthanum Carbonate; Drug: Nicotinamide Placebo |
| Lanthanum Placebo + Nicotinamide | Active comparator | Lanthanum Carbonate Placebo orally three times daily with meals for 2 weeks and Nicotinamide 750mg orally twice daily for 2 weeks Receives: Drug: Nicotinamide; Drug: Lanthanum Carbonate Placebo |
| Lanthanum Placebo + Nicotinamide Placebo | Placebo comparator | Lanthanum Carbonate Placebo orally three times daily with meals for 2 weeks and Nicotinamide Placebo orally twice daily for 2 weeks Receives: Drug: Lanthanum Carbonate Placebo; Drug: Nicotinamide Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Intact FGF23
Longitudinal change in serum intact FGF23 levels from baseline visit through completion of study.
Measured: Approximately 3 weeks.
Secondary outcomes (2)
Change in Plasma Phosphorus Level
Longitudinal change in plasma phosphorus levels from baseline visit through completion of study.
Measured: Approximately 3 weeks.
Change in 24 Hour Urinary Phosphorus Level
Longitudinal change in 24 hour urinary phosphorus levels from baseline visit through completion of study.
Measured: Approximately 3 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2017
- Study start3 Feb 2016
- Primary completion1 Dec 2017
- Study completion1 Dec 2017
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.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Double blind, randomized, placebo-controlled, 2x2 factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tamara Isakova, Northwestern University
- Investigators
- Tamara Isakova, MD, MMSc, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03136705
- Sponsor's protocol ID
- STU00090161
- Status last verified
- Feb 2024
- First submitted
- 23 Mar 2017
- Last updated
- 23 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-Term Effects of Nicotinamide and Lanthanum Carbonate on Phosphorus Homeostasis in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03136705
- Acronym / sponsor ID
- STU00090161
- Conditions
- Healthy
- Keywords
- Phosphorus Homeostasis, FGF23, Vitamin D
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- 3 Feb 2016 (actual)
- Primary completion
- 1 Dec 2017 (actual)
- Study completion
- 1 Dec 2017 (actual)
- First posted
- 2 May 2017 (actual)
- Results
- Posted 23 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
STUDY SUMMARY Title: EFFECTS OF NICOTINAMIDE AND LANTHANUM CARBONATE ON PHOSPHORUS HOMEOSTASIS Protocol Number:STU00090161 Phase: Phase 1, detailed physiologic study Methodology: double blind, randomized, placebo-controlled, 2x2 factorial Study Duration: 12-18 months (to complete the entire study protocol) Study Center: Single-center Objectives: Define short-term effects of the interventions (lanthanum carbonate and nicotinamide) on indices of phosphate handling Number of Subjects: 80 Diagnosis and Main Inclusion Criteria: Healthy volunteers Study Product(s), Dose,Route, Regimen: Nicotinamide, 750 mg by mouth twice daily, Lanthanum carbonate, Fosrenol, 1000 mg by mouth three times daily with meals Duration of administration: 2 weeks (length of time study participants are enrolled in study) Reference therapy: reference is a placebo Statistical Methodology: Repeated measures analysis using mixed linear models
Detailed description
Chronic kidney disease (CKD) is a growing public health problem that increases risks of endstage renal disease (ESRD), cardiovascular disease (CVD), fractures, and death, and it poses an enormous financial burden on the US health system. Existing therapies modestly impact outcomes. Novel strategies targeting CKD-specific mechanisms are urgently needed to improve health and reduce cost.
CKD is complicated by disordered mineral metabolism, characterized by abnormal calcium and phosphate homeostasis, calcitriol and klotho deficiency, and elevated levels of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Elevated FGF23 is the earliest and most common manifestation of disordered mineral metabolism. Observational studies report independent associations between elevated phosphate and FGF23 blood levels and increased risks of ESRD, CVD and death. As potential explanatory mechanisms, phosphate excess induces arterial stiffness due to vascular calcification, and FGF23 excess contributes directly to the pathogenesis of left ventricular hypertrophy (LVH). Together, these effects promote CVD events and death.
Dietary phosphate absorption is a modifiable determinant of phosphate and FGF23 levels. Small studies of short duration suggest that phosphate binders and dietary phosphate modification in CKD can lower phosphate and FGF23 blood levels by reducing paracellular absorption of phosphate in the gut. However, animal studies demonstrate that compensatory upregulation of transcellular phosphate absorption via the sodium phosphate co-transporter, NPT2b, reduces the efficacy of these approaches. Since nicotinamide lowers plasma phosphate by reducing gut expression of NPT2b,the investigators hypothesize that use of nicotinamide combined with phosphate binders on a background of dietary phosphate moderation will most effectively reduce phosphate and FGF23 blood levels in CKD. The investigators plan to advance this approach in future randomized clinical trials.
The objective of this study is to perform a detailed physiologic study of healthy volunteers to assess the short-term effects of nicotinamide alone, lanthanum carbonate alone, or both in combination, on phosphate homeostasis. The results from healthy volunteers will provide information needed for optimal design of studies for patients with CKD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Double blind, randomized, placebo-controlled, 2x2 factorial
| Arm | Type | Receives |
|---|---|---|
| Lanthanum + Nicotinamide | Active comparator | Drug: Nicotinamide, Drug: Lanthanum CarbonateLanthanum Carbonate 1000mg orally three times daily with meals for 2 weeks and Nicotinamide 750mg orally twice daily for 2 weeks |
| Lanthanum + Nicotinamide Placebo | Active comparator | Drug: Lanthanum Carbonate, Drug: Nicotinamide PlaceboLanthanum Carbonate 1000mg orally three times daily with meals for 2 weeks and Nicotinamide Placebo orally twice daily for 2 weeks |
| Lanthanum Placebo + Nicotinamide | Active comparator | Drug: Nicotinamide, Drug: Lanthanum Carbonate PlaceboLanthanum Carbonate Placebo orally three times daily with meals for 2 weeks and Nicotinamide 750mg orally twice daily for 2 weeks |
| Lanthanum Placebo + Nicotinamide Placebo | Placebo comparator | Drug: Lanthanum Carbonate Placebo, Drug: Nicotinamide PlaceboLanthanum Carbonate Placebo orally three times daily with meals for 2 weeks and Nicotinamide Placebo orally twice daily for 2 weeks |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- Healthy volunteers
- Age ≥ 18 years, at the time of screening
- Normal renal function at screening, as defined by
- eGFR > 60
- no albuminuria
Key exclusion criteria (17 listed)
- History of allergic reaction to nicotinamide, niacin (excluding flushing), and/or multivitamin preparations
- Liver disease, defined as known cirrhosis by imaging or physician diagnosis.
- Documented alcohol use > 14 drinks/week
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and/or alkaline phosphatase concentrations > 2 times the upper limit of the local laboratory reference range and/or total bilirubin concentration not within institutional limits.
- Creatine kinase (CK) concentrations > 2 times the upper limit of the local laboratory reference range at screening
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 |
|---|---|---|
| NicotinamideNicotinamide tablet | Drug | Lanthanum + Nicotinamide, Lanthanum Placebo + Nicotinamide |
| Lanthanum CarbonateAlso: FosrenolLanthanum Carbonate tablet | Drug | Lanthanum + Nicotinamide, Lanthanum + Nicotinamide Placebo |
| Lanthanum Carbonate PlaceboAlso: Placebo (for Lanthanum Carbonate 500mg tablet)Sugar pill manufactured to look like Lanthanum Carbonate tablet | Drug | Lanthanum Placebo + Nicotinamide, Lanthanum Placebo + Nicotinamide Placebo |
| Nicotinamide PlaceboAlso: Placebo (for Nicotinamide 750mg tablet)Sugar pill manufactured to look like Nicotinamide tablet | Drug | Lanthanum + Nicotinamide Placebo, Lanthanum Placebo + Nicotinamide Placebo |
Primary outcome
Change in Intact FGF23
Time frame: Approximately 3 weeks.
Longitudinal change in serum intact FGF23 levels from baseline visit through completion of study.
2 secondary outcomes
Change in Plasma Phosphorus Level
Time frame: Approximately 3 weeks.
Change in 24 Hour Urinary Phosphorus Level
Time frame: Approximately 3 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Tamara Isakova, MD, MMSc principal investigator
Northwestern University
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 Nicotinamide and Lanthanum Carbonate in people with Healthy, run by Northwestern University 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 16 inclusion and 17 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 23 Feb 2024. 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. Some participants in this study may receive a placebo. 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 23 Feb 2024). 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 Intact FGF23 (time frame: Approximately 3 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 23 Feb 2024.