FAST GFR: Pilot Study to Evaluate the Safety of the FAST GFR Test in Patients.

A Single-Center Prospective Study Evaluating the FAST Measured Glomerular Filtration Rate (mGFR) Test™ in Adults With Preserved Kidney Function and Impaired Kidney Function With Comparison to Iohexol Clearance Methods

This is a single site study designed to evaluate the FAST mGFR Test™ in healthy adult volunteers, patients with varying degrees of chronic kidney disease (CKD), and patients with acute kidney injury (AKI).

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Acute Kidney Injury
• Intervention / Treatment: Device: 75 mg / 6 mL VFI™

Detailed Description

A rapid and accurate measurement of glomerular filtration rate (GFR) is important in acute kidney injury (AKI) and chronic kidney disease (CKD) for assessment of impairment, diagnosis, and prompt treatment. FAST BioMedical is an emerging technology company whose mission is to quantify clinically meaning ful physiological parameters that have been difficult or impossible to measure. GFR is the most clinically relevant metric for understanding renal function, as it is the rate by which the kidney is able to filter waste products in the bloodstream. The FAST mGFR is for direct measurement of GFR that relies on reading the ratio of fluorescent markers attached to different size dextran molecules introduced into the bloodstream. The test is intended as an adjunct to current methods utilized to assess kidney function.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0007
      • University of Alabama Birmingham, Division of Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for Groups 1-3:

• Female subjects: women must have a negative urine pregnancy test at screening and before dosing on Visit 2 and be either confirmed by the Investigator to be infertile or using a reliable method of contraception Male subjects: reproductively active men must agree to either practice abstinence or utilize adequate contraception.
• Ages 19 to 75
• Subject's screening must fall into one of the available categories of estimated glomerular filtration rate (eGFR) renal function: ≥ 60 mL/min for stage normal function; 30-59 mL/min for stage 3, moderate CKD; 15-29 mL/min for stage 4, severe CKD,
• Patients must not be on inotropes or vasopressors, and must be absent of significant hemodynamic instabilities.

• Patients must have ceased use of the following:

  • nonsteroidal anti-inflammatory drugs - 6 days prior,
  • herbal supplements - 6 days prior to testing and
  • cimetidine and trimethoprim - 14 days prior to testing.
• Ability to comply with study conditions

Inclusion Criteria for Group 4:

- Female subjects; women must have a negative urine pregnancy test at screening and before dosing on Visit 2 and be either confirmed by the Investigator to be infertile or using a reliable method of contraception.

Male subjects: reproductively active men must agree to either practice abstinence or utilize adequate contraception.

• Ages 19 to 75
• For cohort 4: patients diagnosed with [either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI]
• Patients must not be on inotropes or vasopressors, and must be absent of significant hemodynamic instabilities.
• Patients must be without evidence of clinically significant liver dysfunction
• Ability to comply with study conditions

Exclusion Criteria for Groups 1-3:

• Positive history of any clinically significant allergic or negative reactions, side effects, or anaphylaxis to sulfa, iodine, dyes, shellfish, isotopes or dextran molecules
• Previous history of nephrectomy or kidney transplant
• A body weight below 40kg
• A body mass index <17 or >40
• Subjects using Coumadin (Warfarin) who have an INR >4 at Screening or pre-dose on Visit 2
• Past history of liver disease or screening Liver Function tests which exceed 1.5 times the upper limit of normal or an albumin of < 2mg/dl.
• Clinically significant illness within 4 weeks or a clinically significant infection within 4 weeks of screening
• Received blood, donated blood, have clinically significant on-going bleeding, changing haemoglobin, or experienced significant blood loss within 2 weeks of dosing
• Subjects with significant abnormal findings upon physical examination, vital signs, ECG, or clinical laboratory results at Screening
• Subjects with a supine blood pressure after resting for at least 5 minutes outside the 90-145 (systolic) or mmHg or 50-95 mmHg (diastolic) range
• Subjects with a supine (ECG) heart rate outside 45-105 beats/min after resting for at least 5 minutes.
• Subjects with a known or suspected history of drug or alcohol misuse within 6 months prior to screening, subjects who have consumed alcohol within 48 hours of dosing, or subjects who the Investigator believes to be unfit to participate in the study due to abuse of illegal or controlled substances.
• Subjects who had a positive result for Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb) screen.
• Subjects who have been diagnosed with acquired immune deficiency syndrome (AIDS), or test positive for human immunodeficiency virus (HIV).
• Subjects who participated in another clinical trial less than 1 month prior to dosing, or who are currently enrolled in another clinical trial.

• Subjects who have any condition that:

  • Would make him/her, in the opinion of the Investigator, unsuitable for the study
  • Whose condition is likely to deteriorate
  • Who, in the opinion of the Investigator, is not likely to complete the study for any reason

Exclusion Criteria for Group 4:

• Positive history of any clinically significant allergic or negative reactions, side effects, or anaphylaxis to sulfa, iodine, dyes, shellfish, isotopes or dextran molecules
• Previous history of nephrectomy or kidney transplant
• A body weight below 40kg
• A body mass index <17 or >40
• Current use of prescribed anticoagulants
• Past history of liver disease or screening Liver Function tests which exceed 1.5 times the upper limit of normal or an albumin of < 2mg/dl.
• Received blood, donated blood, have clinically significant on-going bleeding, changing haemoglobin, or experienced significant blood loss within 2 weeks of dosing
• Subjects with a supine blood pressure after resting for at least 5 minutes outside the 90-145 (systolic) or mmHg or 50-95 mmHg (diastolic) range
• Subjects with a supine (ECG) heart rate outside 45-105 beats/min after resting for at least 5 minutes.
• Subjects with a known or suspected history of drug or alcohol abuse within 6 months prior to admission, who have a positive drug test or alcohol test, or who have consumed alcohol within 24 of testing
• Subjects who had a positive result for Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb) screen.
• Subjects who have been diagnosed with acquired immune deficiency syndrome (AIDS), or test positive for human immunodeficiency virus (HIV).
• Subjects who participated in another clinical trial less than 1 month prior to dosing, or who are currently enrolled in another clinical trial.

• Subjects who have any condition that:

  • Would make him/her, in the opinion of the Investigator, unsuitable for the study
  • Whose condition is likely to deteriorate
  • Who, in the opinion of the Investigator, is not likely to complete the study for any reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
EXPERIMENTAL: Cohort 2; eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
EXPERIMENTAL: Cohort 3; eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
EXPERIMENTAL: Cohort 4; a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
EXPERIMENTAL: Cohort 5; eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product or investigational medical device.	Baseline through day 22
Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product or investigational medical device.	Baseline through day 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	Cmax = maximum observed concentration occurring at Tmax	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	Tmax = time of maximum observed concentration	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	AUClast = area under the concentration-time curve (time 0 to last sample with a quantifiable measurable concentration)	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	AUCall = area under the concentration-time curve (time 0 to last scheduled sample)	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	AUCinf = area under the concentration-time curve (time 0 extrapolated to infinity based on the last observed concentration)	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	T1/2 = terminal half-life = ln(2)/λz	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	Vz = volume of distribution based upon terminal phase	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	Vss = volume of distribution at steady state	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	CL = total body clearance	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	Cmax/Dose = maximum observed concentration occurring at Tmax/Dose	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function	AUCinf/Dose = area under the concentration-time curve (time 0 extrapolated to infinity based on the last observed concentration)/Dose	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.
To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods.	This analysis will compare estimates of kidney function derived from the results of FAST VFI™ to those derived through conventional Iohexol clearance methods.	Baseline through Day 22
To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume.	This analysis will compare estimates of plasma volume derived by FAST's plasma volume method with that derived using the conventional Nadler's Formula for plasma volume.	Baseline through day 22

Collaborators and Investigators

• Sponsor: FAST BioMedical
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Dana V Rizk, M.D, University of Alabama Birmingham, 205-934-9509, drizk@uab.edu

Publications and helpful links

General Publications

• Wang E, Meier DJ, Sandoval RM, Von Hendy-Willson VE, Pressler BM, Bunch RM, Alloosh M, Sturek MS, Schwartz GJ, Molitoris BA. A portable fiberoptic ratiometric fluorescence analyzer provides rapid point-of-care determination of glomerular filtration rate in large animals. Kidney Int. 2012 Jan;81(1):112-7. doi: 10.1038/ki.2011.294. Epub 2011 Aug 31.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: October 25, 2013
• First Submitted That Met QC Criteria: October 31, 2013
• First Posted (ESTIMATE): November 7, 2013

Study Record Updates

• Last Update Posted (ACTUAL): December 12, 2017
• Last Update Submitted That Met QC Criteria: November 13, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; CKD; Acute Kidney Injury; organ function; Blood volume; Renal function; kidney function; AKI; renal disease; GFR; Glomerular Filtration Rate; Plasma Volume; mGFR; measured GFR; kidney biomarker; renal biomarker; kidney monitor; kidney device
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Acute Kidney Injury
• Other Study ID Numbers: FAST mGFR -002; 1R44DK093274-01 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED