Safety and Tolerability Study of Inhaled Carbon Monoxide in Kidney Transplant Patients

A Prospective, Multicenter, Single-blind, Placebo-controlled, Safety and Tolerability Study of the Effects of Carbon Monoxide for Inhalation in Patients Receiving Kidney Transplants.

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.

Study Overview

• Status: Withdrawn
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Inhaled carbon monoxide; Drug: Inhaled carbon monoxide; Drug: Inhaled carbon monoxide; Drug: Inhaled Carbon Monoxide; Drug: Inhaled Carbon Monoxide

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
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	28 days

Collaborators and Investigators

• Sponsor: Mallinckrodt

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: September 18, 2007
• First Submitted That Met QC Criteria: September 18, 2007
• First Posted (Estimate): September 19, 2007

Study Record Updates

• Last Update Posted (Estimate): October 19, 2016
• Last Update Submitted That Met QC Criteria: October 18, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Kidney Transplant, Carbon Monoxide
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gasotransmitters; Carbon Monoxide
• Other Study ID Numbers: C201