Ubiquinol (Reduced COQ10) for Patients With Sepsis

• ClinicalTrials.gov Identifier: NCT01948063
• Recruitment Status: Completed
• First Posted: September 23, 2013
• Results First Posted: April 24, 2017
• Last Update Posted: April 24, 2017
• Sponsor: Beth Israel Deaconess Medical Center
• Collaborator: Kaneka Medical America LLC
• Information provided by (Responsible Party): Michael Donnino, Beth Israel Deaconess Medical Center

Study Description

Brief Summary:

This study aims to determine if Ubiquinol (reduced form of COQ10) will attenuate mitochondrial injury and decrease inflammatory response in patients suffering from sepsis.

Condition or disease	Intervention/treatment	Phase
Sepsis	Drug: Ubiquinol; Dietary Supplement: Placebo	Phase 2

Detailed Description:

Severe sepsis and septic shock are the cause of significant morbidity and mortality worldwide. An estimated 751,000 (3 per 1,000 population) cases of severe sepsis occur in the United States each year, resulting in approximately 215,000 deaths. Septic shock is characterized by hypotension, hypermetabolic state, lactic acidosis, and potentially death. In addition, the economic burden on the health care system for patients suffering from severe sepsis is striking. Weycker et al. report that patients suffering from severe sepsis will require an average of $45,000 dollars of medical care cost on their index admission and up to $78,500 dollars in the first year post-diagnosis. These figures rival such entities as acute myocardial infarction, trauma, and stroke. Whereas a significant amount of research and therapeutic interventions have been focused on the "early hours" of diseases such as acute myocardial infarction, stroke, and trauma, less attention has been given to the initial stages of severe sepsis and septic shock.

Coenzyme Q10 (CoQ10) is a safe and feasible medicinal intervention with a strong scientific rationale for use in septic shock. CoQ10 is a key component of the mitochondria, serving as an electron transport medium between complex I/II and complex III. A lesion at this point in the electron transport chain results in an inadequate production of ATP (adenosine triphosphate) for the cell. In septic shock, CoQ10 levels are profoundly decreased and therefore production of energy may be compromised. CoQ10 has two essential roles in critically ill patients with sepsis: 1) production of ATP and 2) reduction of free oxygen radicals. CoQ10's key role in the electron transport chain may prevent the well-described mitochondrial dysfunction that occurs in patients with septic shock. Thus, these two essential roles form the pathophysiological basis for this proposed study.

In the following proposal, the investigators plan to perform a pilot study to evaluate the capacity for ubiquinol (reduced form of COQ10) to attenuate mitochondrial injury, to attenuate inflammation/vascular endothelial injury, the effect on the human metabolome, and to be absorbed. The overall goal of this line of research will be to determine if CoQ10 will attenuate oxidative injury and improve mitochondrial function leading to overall improved outcome in patients suffering from septic shock. In order to achieve this long-term goal, the investigators propose this pilot and feasibility trial to determine CoQ10 absorption in critical illness, capacity to mitigate inflammatory injury and oxidative injury, and ability to maintain mitochondrial electron transport chain functionality. This pilot study will also provide key feasibility data on blinding and other logistical issues necessary for execution of a larger-scale investigation.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Ubiquinol (Reduced COQ10) for Patients With Sepsis
• Study Start Date: October 2012
• Actual Primary Completion Date: April 2014
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control; Depending on the patient's ability to swallow pills, patients in the control group will receive a placebo pill or a liquid placebo, which is 50 milliliters of Ensure (a dietary supplement). This will be given every 12 hours for 7 days or until hospital discharge.	Dietary Supplement: Placebo; Depending on the patient's ability to swallow pills, patients in the control group will receive a placebo pill or a liquid placebo, which is 50 milliliters of Ensure (a dietary supplement). This will be given every 12 hours for 7 days or until hospital discharge.; Other Name: placebo pill or a liquid placebo (Ensure)
Experimental: Ubiquinol; Depending on the patient's ability to swallow pills, patients in the experimental group will receive 200mg of Ubiquinol in either a pill or a liquid. The liquid form of the study med will be mixed with 50 milliliters of Ensure (a dietary supplement) to ensure blinding. This will be given every 12 hours for 7 days or until hospital discharge.	Drug: Ubiquinol; Depending on the patient's ability to swallow pills, patients in the experimental group will receive 200mg Ubiquinol in either a pill or a liquid. The liquid form of the study med will be mixed with 50 milliliters of Ensure (a dietary supplement) to ensure blinding. This will be given every 12 hours for 7 days or until hospital discharge.

Outcome Measures

Primary Outcome Measures :

1. CoQ10 Levels [ Time Frame: 24 hours after study drug administration ]
   Total CoQ10 levels (mcg/mL) at 24 hours post study drug admission.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Over 18 years old
• Suspected or confirmed infection
• Presence of 2 or more systemic inflammatory response syndrome (SIRS) criteria
• Admission to the ICU

Exclusion Criteria:

• Under 18 years old
• Current CoQ10 supplementation
• Unable to receive enteral medications
• Would need a nasogastric or orogastric tube solely for the purposes of the study
• Pregnancy, incarceration, mentally disability
• Patient confirmed Comfort measures only, Do not resuscitate (DNR) and/or Do not intubate. Patients with DNR but intubated and being provided full care are eligible

Contacts and Locations

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

Kaneka Medical America LLC

Investigators

• Principal Investigator: Michael Donnino, MD; Beth Israel Deaconess Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Donnino MW, Mortensen SJ, Andersen LW, Chase M, Berg KM, Balkema J, Radhakrishnan J, Gazmuri RJ, Liu X, Cocchi MN. Ubiquinol (reduced Coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial. Crit Care. 2015 Jul 1;19:275. doi: 10.1186/s13054-015-0989-3.

• Responsible Party: Michael Donnino, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01948063
• Other Study ID Numbers: 2012P000267
• First Posted: September 23, 2013
• Results First Posted: April 24, 2017
• Last Update Posted: April 24, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Sepsis; Toxemia; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes