Caffeinol Hypothermia Protocol

Acute Ischemic Stroke Clinical Trial

Official title:

Combined Neuroprotective Modalities Coupled With Thrombolysis in Acute Ischemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00299416
• Other study ID #: HSC- MS-02-188
• Secondary ID: P50NS44277 proje
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 2, 2006
• Last updated: April 5, 2011
• Start date: February 2003
• Est. completion date: August 2009

Study information

• Verified date: April 2011
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Caffeinol is a combination of caffeine and alcohol. The amount given is about the same as 1-2 glasses of wine and 3-4 cups of coffee. The patient receives a one time dose given over two hour while being cooled to 34.5 C.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age 18-80 years

2. Clinical presentation of acute ischemic stroke

3. Computed tomography (CT) scan compatible with acute ischemic stroke.

4. Time to caffeinol treatment < 240 minutes from stroke onset.

5. Time to hypothermia initiation < 300 minutes from stroke onset.

6. Presumed cortical location of stroke (must have at least on sign such as aphasia, neglect, visual field cut)

7. National Institutes of Health Stroke Scale (NIHSS) > 8 at time of each treatment.

8. Tissue plasminogen activator (TPA) treated patients must meet all established criteria for TPA.

Exclusion Criteria:

1. Etiology other than ischemic stroke.

2. Item 1a on NIHSS > 1

3. Signs/symptoms of subcortical, brainstem or cerebellar stroke.

4. Symptoms resolving or NIHSS < 8 at time of each treatment.

5. NIHSS > 20 if right hemisphere or >25 if left hemisphere

6. Known alcoholic

7. Clinical or laboratory evidence of alcohol intoxication.

8. Historical evidence of exogenous caffeine exposure beyond daily consumption of coffee or soft drinks.

9. Known hematologic dyscrasias that affect thrombosis.

10. Comorbid conditions likely to complicate therapy:

1. End-stage cardiomyopathy

2. Uncompensated or clinically significant arrhythmia

3. Myopathy

4. Liver disease

5. History of pelvic or abdominal mass likely to compress inferior vena cava.

6. End-stage AIDS

7. History of clinically significant gastrointestinal (GI) bleeding

8. Impaired renal function with creatinine clearance, 50 ml/min

11. Intracerebral / intraventricular hemorrhage

12. Systolic blood pressure (SBP) > 210 or < 100; diastolic blood pressure (DBP) > 100 or < 50 mmHg

13. Severe coagulopathy

14. Pregnancy

15. Use of monoamine oxidase inhibitor (MAOI),serotonin-specific reuptake inhibitor (SSRI) or Tricyclic Antidepressants (TCA) within the preceding 2 weeks

16. Known history of epilepsy.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Hypothermia

Intervention

Drug:
• Caffeinol
Infusion of caffeinol (9mg/kg caffeine + 0.4g/kg ethanol) over 2 hours.

Procedure:
• hypothermia
External or internal cooling for 24 hours and rewarming over 12 hours.

Locations

Country	Name	City	State
United States	Memorial Hermann Hospital - Medical Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Symptomatic Intracerebral Hemorrhage	Symptomatic intracerebral hemorrhages were measured by a full NIHSS(National Institute of Health Stroke Scale) prior to caffeinol & hypothermia,at the end of hypothermia & rewarming, 24 hrs after stroke onset, daily during hospitalization,& at the 90 day follow-up visit. In addition, modified NIHSS were done hourly during the 24 hr hypothermia period & 12 hr rewarming period. At the end of rewarming an MRI was obtained to verify if hemorrhages or neurologic deteriorations were present.NIHSS scores severity of stroke on 11 items;more points given for greater deficiencies(range 0-42,0=normal)	from pre-dosage to 90 day followup	Yes
Primary	Number of Participants With Catheter Related Complications During Hypothermia & Rewarming	Catheter-related complications assessed whether participants had bleeding (major hemorrhaging) that required a blood transfusion, this was determined by labs. Participants were monitored for infections every hour during vital signs in the 24 hour hypothermia phase and 12 hour rewarming phase.	over 36 hour period	Yes
Primary	Number of Participants With Cardiorespiratory Failure	The possibility of cardiorespiratory failure was monitored every 30 minutes during the 24 hour hypothermia period based on vitals signs and oxygen saturation.	every 30 minutes during hypothermia induction	Yes
Secondary	Feasibility: Time Required to Reach the Target Core Temperature or Lowest Tolerated Temperature, Stability of Patient Temperature, Control of Rewarming,	Hypothermia will be maintained for 24 hours, afterward, the patient will be rewarmed, gradually, over 12 hours to 36.5C.	rewarming over 12 hours until 36.5C has been achieved	No
Secondary	Achievement of Therapeutic Serum Ethanol and Caffeine Levels, and Amount of Sedation Needed to Suppress Shivering.		rewarming over 12 hours until 36.5C has been achieved	Yes
Secondary	Efficacy: NIHSS < 2 at 24 Hours, Modified Rankin Scale (mRS) < 2 at 3 Months, NIHSS < 2 at 3 Months, and Length of Hospital and ICU Stay.	NIHSS score of = 2 24 hours after stroke onset modified Rankin Scale (mRS) < 2 at 90 day followup NIHSS score of = 2 at daily duration of hospitalization and ICU stay and 90 day follow up.	90 days	No

External Links

•   Introduction of the staff and facility on the stroke team, types of strokes, treatment, risk factors, recovery clinical trials, and contact information.