Safety and Tolerability Study of Inhaled Carbon Monoxide in Kidney Transplant Patients - Full Text View

Sponsor:	INO Therapeutics
Information provided by:	INO Therapeutics
ClinicalTrials.gov Identifier:	NCT00531856

Purpose

The purpose of this study is to evaluate the safety and tolerability of two carbon monoxide doses when administered as an inhaled gas for 1 hour in patients receiving kidney transplants.

Condition	Intervention	Phase
Kidney Transplantation	Drug: Inhaled carbon monoxide Drug: Inhaled Carbon Monoxide	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Basic Science
Official Title:	A Prospective, Multicenter, Single-blind, Placebo-controlled, Safety and Tolerability Study of the Effects of Carbon Monoxide for Inhalation in Patients Receiving Kidney Transplants.

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Carbon monoxide

U.S. FDA Resources

Further study details as provided by INO Therapeutics:

Primary Outcome Measures:

Evaluate the safety and tolerability of three carbon monoxide dose levels when administered as an inhaled gas for 1 hour in patients receiving kidney transplants [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Characterize the pharmacokinetics of the inhaled carbon monoxide; Correlate the safety parameters to inhaled carbon monoxide and COHb levels; Assess laboratory values; Assess potential markers for the incidence of delayed graft function [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	August 2007
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 5.97 mg/L of carbon monoxide in 30% oxygen	Drug: Inhaled carbon monoxide 0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant Drug: Inhaled carbon monoxide 2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant Drug: Inhaled carbon monoxide 3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant Drug: Inhaled Carbon Monoxide 3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant Drug: Inhaled Carbon Monoxide 2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.
Placebo Comparator: 2 Oxygen 30% in Nitrogen	Drug: Inhaled carbon monoxide 0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant Drug: Inhaled carbon monoxide 2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant Drug: Inhaled carbon monoxide 3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant Drug: Inhaled Carbon Monoxide 3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant Drug: Inhaled Carbon Monoxide 2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.

Arms

Assigned Interventions

Experimental: 1

5.97 mg/L of carbon monoxide in 30% oxygen

Drug: Inhaled carbon monoxide

0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Drug: Inhaled carbon monoxide

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Drug: Inhaled carbon monoxide

3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Drug: Inhaled Carbon Monoxide

3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Drug: Inhaled Carbon Monoxide

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.

Placebo Comparator: 2

Oxygen 30% in Nitrogen

Drug: Inhaled carbon monoxide

0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Drug: Inhaled carbon monoxide

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Drug: Inhaled carbon monoxide

3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Drug: Inhaled Carbon Monoxide

3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Drug: Inhaled Carbon Monoxide

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.

Detailed Description:

The mechanisms by which carbon monoxide exerts its effects in preventing damage of the graft appear to vary among the models and organs with the common theme of carbon monoxide acting as a potent anti-inflammatory molecule. Carbon monoxide affects several intracellular signaling pathways. In addition, carbon monoxide generates increased levels of anti-inflammatory molecules.

Evaluate the safety and tolerability of three carbon monoxide dose levels consisting of a single 0.7 mg/kg dose and a single 2.0 mg/kg dose when administered post-operatively and a single 2.0 mg/kg dose, a single 3.0mg/kg dose and a 3.5 mg/kg dose when administered intra-operatively as an inhaled gas for 1 hour, by assessment of adverse events (AEs), vital signs, laboratory variables, serum carboxyhemoglobin (COHb), oxygenation, electrocardiography (ECG), and neurocognitive status in patients receiving kidney transplants.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female receiving a kidney transplant from any donor type
BMI between 16 and 36 inclusive
Spontaneously breathing (non-intubated) with supplemental oxygen standardized at 2 liters via nasal cannula
Hemodynamically stable with a systolic arterial pressure > 90 mmHg and a heart rate < 120 beats/min
Acceptable transplantation candidate as judged by medical history, physical exam, ECG, vital signs, clinical chemistry, hematology, and urinalysis
Given written and verbal information and had the opportunity to ask questions about the study
Signed informed consent to participate in the study

Exclusion Criteria:

Exposure to any carbon monoxide source (e.g., fire, gas, or heavily polluted air) during the 48 hours prior to the study day
Baseline blood level of COHb >2%
Baseline hemoglobin (Hb) <10.0 g/dL
Patients with significant underlying lung disease such as moderate or severe asthma, COPD, and interstitial lung disease
Baseline oxygen saturation <95%
Pregnancy or breastfeeding
Participation in other clinical trial within 2 months prior to study drug treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531856

Locations

United States, California
Universtiy of CA, San Francisco
San Francisco, California, United States, 94143
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

INO Therapeutics

More Information

No publications provided

Responsible Party:	Alyssa Hill, INO Therapeutics
ClinicalTrials.gov Identifier:	NCT00531856 History of Changes
Other Study ID Numbers:	C201
Study First Received:	September 18, 2007
Last Updated:	August 26, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by INO Therapeutics:

Kidney Transplant, Carbon Monoxide

Additional relevant MeSH terms:

Carbon Monoxide
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012