Coenzyme Q10 in Post-Cardiac Arrest Cerebral Resuscitation

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01319110
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Specific Aim #1: To determine if levels of CoQ10 are low post-cardiac arrest (CA). We will perform a prospective trial with the primary endpoint of describing the prevalence of low serum CoQ10 levels.

Specific Aim #2: To determine if CoQ10 levels in post-CA patients can be increased with the administration of exogenous CoQ10.. We will perform a randomized control trial (RCT) of post-CA patients with the secondary endpoint of comparing CoQ10 levels among those randomized to CoQ10 supplementation vs placebo.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest; Sudden Cardiac Arrest	Drug: Coenzyme Q10; Dietary Supplement: Placebo	Phase 2

Detailed Description

Cardiac arrest (CA) occurs in nearly 350,000 patients in the U.S. each year with an estimated mortality of 60% in those surviving the initial arrest. Moreover, the overall prognosis for survivors is often limited by neurologic injury. Two randomized control trials (RCTs) have demonstrated that therapeutic hypothermia (TH) after CA improves survival and reduces neurologic morbidity. As a result of these studies, TH has become the standard of care in post-CA patients. The mechanism of action for TH is hypothesized to be a reduction in cerebral oxygen consumption that occurs following an ischemia-reperfusion injury. Another similar potential target following ischemia-reperfusion injury is mitochondrial function in the injured brain cells and attenuation of potentially damaging oxygen-free radicals. Specifically, optimizing mitochondrial function and reducing oxygen free radicals may enhance cellular function and mitigate cellular injury thereby leading to improved neurologic outcomes. Coenzyme Q10 (CoQ10) is an essential mitochondrial co-factor and free radical scavenger that has been found to have neuroprotective effects in various neurodegenerative disorders such as Parkinson's disease and Huntington's disease. Whether CoQ10 can provide neuroprotection in acute ischemia-reperfusion injury remains less clear, but has been recognized by the American Heart Association as a potentially promising neuroprotective agent. We hypothesize that the administration of exogenous CoQ10 will raise serum concentrations of CoQ10 and as such may mitigate the adverse effects of the post-CA ischemia-reperfusion injury on the brain by optimizing mitochondrial function and reducing oxygen-free radicals. We support this hypothesis by the following:

1. Ischemia-reperfusion injury disrupts normal mitochondrial function and increases O2 free radicals.

2. CoQ10 has been found to attenuate the effects of ischemia-reperfusion injury through optimizing mitochondrial function and mitigation of cellular apoptosis.

3. CoQ10 has neuroprotective effects in other neurodegenerative disorders.

4. Our group has unpublished preliminary data showing low CoQ10 levels in a majority of patients with septic shock, and that lower CoQ10 levels are significantly associated with multiple markers of the inflammatory cascade.

5. A pilot human trial in post-CA patients demonstrated a reduction in mortality and trend toward reduction in neurologic morbidity.

To test our hypothesis, we propose the following pilot study as proof of concept in preparation for a larger multicenter trial powered toward neurologic outcome and mortality. This pilot study will allow for a more informed power analysis for a larger trial, provide proof of concept for enrollment and administration of therapy, examine the time-frame for drug absorption into serum, and evaluate for tolerability.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Coenzyme Q10 in Post-Cardiac Arrest Cerebral Resuscitation
• Actual Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Dec 31, 2011
• Actual Study Completion Date: Dec 31, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CoenzymeQ10 Patients will receive CoenzymeQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.	Drug: Coenzyme Q10; Patients will receive CoQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.; Other Names: Ubiquinone
Placebo Comparator: Placebo Patients will receive 20 ml chocolate Ensure (as a placebo) three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). Placebo will be given through pre-existing NG or OG tube.	Dietary Supplement: Placebo; Patients will be given Chocolate Ensure via NG/ OG 3x daily as a placebo.

Outcome Measures

Primary Outcome Measures

1. Prevalence of Low Serum CoQ10 Levels in Cardiac Arrest Patients [Baseline]

   The primary outcome will be describing the prevalence of low serum CoQ10 levels compared to standard laboratory control values.

Secondary Outcome Measures

1. Comparison of Serum CoQ10 Levels Randomized to Supplementation vs. Placebo [1 year]

   The secondary outcome will be to compare serum CoQ10 levels among those post-arrest patients randomized to CoQ10 supplementation vs placebo.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult patients (age > 18 years)

2. Comatose after CA with subsequent return of spontaneous circulation

Exclusion Criteria:

1. Comatose status prior to CA

2. CoQ10 therapy within one month prior to CA

3. Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center

Investigators

• Principal Investigator: Michael N Cocchi, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Beth Israel Deaconess Medical Center Cardiac Arrest Center

Publications

None provided.

• Responsible Party: Michael N. Cocchi, MD, Principal Investigator, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01319110
• Other Study ID Numbers: 2010P000362
• First Posted: Mar 21, 2011
• Last Update Posted: Jul 31, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Michael N. Cocchi, MD, Principal Investigator, Beth Israel Deaconess Medical Center: Cardiac Arrest; Post Cardiac Arrest; CoQ10; Ubiquinone; Post Arrest
• Additional relevant MeSH terms: Heart Arrest; Death, Sudden, Cardiac; Ubiquinone; Coenzyme Q10

Study Results

Participant Flow

Arm/Group Title	CoenzymeQ10	Placebo
Arm/Group Description	Patients will receive CoenzymeQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff. Coenzyme Q10: Patients will receive CoQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.	Patients will receive 20 ml chocolate Ensure (as a placebo) three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). Placebo will be given through pre-existing NG or OG tube. Placebo: Patients will be given Chocolate Ensure via NG/ OG 3x daily as a placebo.
Period Title: Overall Study
STARTED	5	5
COMPLETED	5	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	CoenzymeQ10	Placebo	Total
Arm/Group Description	Patients will receive CoenzymeQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff. Coenzyme Q10: Patients will receive CoQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.	Patients will receive 20 ml chocolate Ensure (as a placebo) three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). Placebo will be given through pre-existing NG or OG tube. Placebo: Patients will be given Chocolate Ensure via NG/ OG 3x daily as a placebo.	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 80%	5 100%	9 90%
>=65 years	1 20%	0 0%	1 10%
Sex: Female, Male (Count of Participants)
Female	1 20%	2 40%	3 30%
Male	4 80%	3 60%	7 70%

Outcome Measures

1. Primary Outcome

Title	Prevalence of Low Serum CoQ10 Levels in Cardiac Arrest Patients
Description	The primary outcome will be describing the prevalence of low serum CoQ10 levels compared to standard laboratory control values.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CoenzymeQ10	Placebo
Arm/Group Description	Patients will receive CoenzymeQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff. Coenzyme Q10: Patients will receive CoQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.	Patients will receive 20 ml chocolate Ensure (as a placebo) three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). Placebo will be given through pre-existing NG or OG tube. Placebo: Patients will be given Chocolate Ensure via NG/ OG 3x daily as a placebo.
Measure Participants	5	5
Mean (Standard Deviation) [ug/mL]	0.706 (0.290137)	0.66 (0.267955)

2. Secondary Outcome

Title	Comparison of Serum CoQ10 Levels Randomized to Supplementation vs. Placebo
Description	The secondary outcome will be to compare serum CoQ10 levels among those post-arrest patients randomized to CoQ10 supplementation vs placebo.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

This data was not collected when the study was performed

Arm/Group Title	CoenzymeQ10	Placebo
Arm/Group Description	Patients will receive CoenzymeQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff. Coenzyme Q10: Patients will receive CoQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.	Patients will receive 20 ml chocolate Ensure (as a placebo) three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). Placebo will be given through pre-existing NG or OG tube. Placebo: Patients will be given Chocolate Ensure via NG/ OG 3x daily as a placebo.
Measure Participants	0	0

Adverse Events

Arm/Group Title	CoenzymeQ10		Placebo
Arm/Group Description	Patients will receive CoenzymeQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff. Coenzyme Q10: Patients will receive CoQ10 200mg three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). CoQ10 will be given through pre-existing NG or OG tube, and mixed with 20 ml of chocolate Ensure so as to blind investigators and staff.		Patients will receive 20 ml chocolate Ensure (as a placebo) three times per day for 7 days, until return to baseline neurologic status, or until death/discharge (whichever comes first). Placebo will be given through pre-existing NG or OG tube. Placebo: Patients will be given Chocolate Ensure via NG/ OG 3x daily as a placebo.
All Cause Mortality
	CoenzymeQ10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CoenzymeQ10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		2/5 (40%)
General disorders
Death	2/5 (40%)	2	2/5 (40%)	2
Other (Not Including Serious) Adverse Events
	CoenzymeQ10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		0/5 (0%)
Gastrointestinal disorders
Gut suctioning	1/5 (20%)	1	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.