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Healthy Combine Study

Sponsor
Northwestern University (Other)
Overall Status
Completed
CT.gov ID
NCT03136705
Collaborator
(none)
39
Enrollment
1
Location
4
Arms
21.9
Actual Duration (Months)
1.8
Patients Per Site Per Month

Study Details

Study Description

Brief 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 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

Condition or Disease Intervention/Treatment Phase
  • Drug: Nicotinamide
  • Drug: Lanthanum Carbonate
  • Drug: Lanthanum Carbonate Placebo
  • Drug: Nicotinamide Placebo
 Phase 1

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

Study Type:
Interventional
Actual Enrollment :
39 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Intervention Model Description:
Double blind, randomized, placebo-controlled, 2x2 factorialDouble blind, randomized, placebo-controlled, 2x2 factorial
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Short-Term Effects of Nicotinamide and Lanthanum Carbonate on Phosphorus Homeostasis in Healthy Volunteers
Actual Study Start Date :
Feb 3, 2016
Actual Primary Completion Date :
Dec 1, 2017
Actual Study Completion Date :
Dec 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Lanthanum + Nicotinamide

Lanthanum Carbonate 1000mg orally three times daily with meals for 2 weeks and Nicotinamide 750mg orally twice daily for 2 weeks

Drug: Nicotinamide
Nicotinamide tablet

Drug: Lanthanum Carbonate
Lanthanum Carbonate tablet
Other Names:
  • Fosrenol

    		•
    Active Comparator: Lanthanum + Nicotinamide Placebo

    Lanthanum Carbonate 1000mg orally three times daily with meals for 2 weeks and Nicotinamide Placebo orally twice daily for 2 weeks

    Drug: Lanthanum Carbonate
    Lanthanum Carbonate tablet
    Other Names:
  • Fosrenol

    • Drug: Nicotinamide Placebo
    Sugar pill manufactured to look like Nicotinamide tablet
    Other Names:
  • Placebo (for Nicotinamide 750mg tablet)

    		•
    Active Comparator: Lanthanum Placebo + Nicotinamide

    Lanthanum Carbonate Placebo orally three times daily with meals for 2 weeks and Nicotinamide 750mg orally twice daily for 2 weeks

    Drug: Nicotinamide
    Nicotinamide tablet

    Drug: Lanthanum Carbonate Placebo
    Sugar pill manufactured to look like Lanthanum Carbonate tablet
    Other Names:
  • Placebo (for Lanthanum Carbonate 500mg tablet)

    		•
    Placebo Comparator: Lanthanum Placebo + Nicotinamide Placebo

    Lanthanum Carbonate Placebo orally three times daily with meals for 2 weeks and Nicotinamide Placebo orally twice daily for 2 weeks

    Drug: Lanthanum Carbonate Placebo
    Sugar pill manufactured to look like Lanthanum Carbonate tablet
    Other Names:
  • Placebo (for Lanthanum Carbonate 500mg tablet)

    • Drug: Nicotinamide Placebo
    Sugar pill manufactured to look like Nicotinamide tablet
    Other Names:
  • Placebo (for Nicotinamide 750mg tablet)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in FGF23 [Approximately 3 weeks.]

      Longitudinal change in serum FGF23 levels from baseline visit through completion of study.

    Secondary Outcome Measures

    1. Change in PTH [Approximately 3 weeks.]

      Longitudinal change in serum PTH levels from baseline visit through completion of study.

    2. Change in plasma phosphorus level [Approximately 3 weeks.]

      Longitudinal change in plasma phosphorus levels from baseline visit through completion of study.

    3. Change in urinary phosphorus level [Approximately 3 weeks.]

      Longitudinal change in urinary phosphorus levels from baseline visit through completion of study.

    4. Change in P1NP [Approximately 3 weeks.]

      Longitudinal change in serum P1NP levels from baseline visit through completion of study.

    5. Change in CTX [Approximately 3 weeks.]

      Longitudinal change in urinary phosphorus levels from baseline visit through

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    INCLUSION CRITERIA

    Healthy volunteers

    Age ≥ 18 years, at the time of screening

    Normal renal function at screening, as defined by

    • eGFR > 60

    • no albuminuria

    • normal urinalysis

    • 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.

    EXCLUSION CRITERIA:

    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.

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Center for Translational Metabolism and Health (CTMH), Northwestern University Chicago Illinois United States 60611

    Sponsors and Collaborators

    • Northwestern University

    Investigators

    • Principal Investigator: Tamara Isakova, MD, MMSc, Northwestern University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Tamara Isakova, Associate Professor Department of Medicine-Nephrology, Director of the Center for Translational Metabolism and Health, Northwestern University
    ClinicalTrials.gov Identifier:
    NCT03136705
    Other Study ID Numbers:
    • STU00090161
    First Posted:
    May 2, 2017
    Last Update Posted:
    Dec 22, 2017
    Last Verified:
    Dec 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Tamara Isakova, Associate Professor Department of Medicine-Nephrology, Director of the Center for Translational Metabolism and Health, Northwestern University
    Phosphorus Homeostasis
    FGF23
    Vitamin D
    Additional relevant MeSH terms:
    Niacinamide
    Niacin
    Nicotinic Acids

    Study Results

    No Results Posted as of Dec 22, 2017