Healthy Combine Study

NCT ID: NCT03136705

Last Updated: 2024-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-03
• Study Completion Date: 2017-12-01

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

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Lanthanum + Nicotinamide

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

Group Type: ACTIVE_COMPARATOR

Nicotinamide

Intervention Type: DRUG

Nicotinamide tablet

Lanthanum Carbonate

Intervention Type: DRUG

Lanthanum Carbonate tablet

Lanthanum + Nicotinamide Placebo

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

Group Type: ACTIVE_COMPARATOR

Lanthanum Carbonate

Intervention Type: DRUG

Lanthanum Carbonate tablet

Nicotinamide Placebo

Intervention Type: DRUG

Sugar pill manufactured to look like Nicotinamide tablet

Lanthanum Placebo + Nicotinamide

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

Group Type: ACTIVE_COMPARATOR

Nicotinamide

Intervention Type: DRUG

Nicotinamide tablet

Lanthanum Carbonate Placebo

Intervention Type: DRUG

Sugar pill manufactured to look like Lanthanum Carbonate tablet

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

Group Type: PLACEBO_COMPARATOR

Lanthanum Carbonate Placebo

Intervention Type: DRUG

Sugar pill manufactured to look like Lanthanum Carbonate tablet

Nicotinamide Placebo

Intervention Type: DRUG

Sugar pill manufactured to look like Nicotinamide tablet

Interventions

Nicotinamide

Nicotinamide tablet

Intervention Type: DRUG

Lanthanum Carbonate

Lanthanum Carbonate tablet

Intervention Type: DRUG

Lanthanum Carbonate Placebo

Sugar pill manufactured to look like Lanthanum Carbonate tablet

Intervention Type: DRUG

Nicotinamide Placebo

Sugar pill manufactured to look like Nicotinamide tablet

Intervention Type: DRUG

Other Intervention Names

Fosrenol; Placebo (for Lanthanum Carbonate 500mg tablet); Placebo (for Nicotinamide 750mg tablet)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Tamara Isakova

Associate Professor Department of Medicine-Nephrology, Director of the Center for Translational Metabolism and Health

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tamara Isakova, MD, MMSc

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Center for Translational Metabolism and Health (CTMH), Northwestern University

Chicago, Illinois, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Study Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STU00090161

Identifier Type: -

Identifier Source: org_study_id