Caffeine and Neurologic Recovery Following Surgery and General Anesthesia

NCT ID: NCT03577730

Last Updated: 2021-10-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

71 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-10

Study Completion Date

2020-01-17

Brief Summary

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The ongoing opioid epidemic is a public health crisis, and surgical patients are particularly vulnerable to opioid-dependency and related risks. Emerging data suggest that caffeine may reduce pain after surgery. Thus, the purpose of this study is to test whether caffeine reduces pain and opioid requirements after surgery. The investigators will also test whether caffeine improves mood and brain function (e.g., learning, memory) after surgery.

Detailed Description

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Opioid-related deaths have quadrupled in the last 20 years, and nearly half of these deaths currently involve prescription opioids. Surgical patients often experience moderate-to-severe pain is common after major surgery, and surgery is associated with a 14-fold increased risk of opioid dependency compared to non-surgical controls, even after minor surgery. Furthermore, mood disorders (e.g., depression) are independently associated with persistent opioid use postoperatively, and signs of postoperative depression are common after major surgery. Thus, given these risk factors, surgical patients are at particularly high risk for opioid dependency postoperatively. Interventions that (1) reduce opioid burden, and (2) improve mood and neuropsychological function may mitigate the risk of postoperative opioid dependency. Preliminary laboratory and clinical findings demonstrate that caffeine may reduce pain after surgery, which may translate to lower opioid requirements. The study tests the hypothesis that intraoperative caffeine administration will improve opioid consumption, pain, and neuropsychological recovery in patients undergoing surgery. Through validated assessment measures, the research team will study the effects of caffeine in relation to postoperative opioid requirements, pain, and neuropsychological (e.g., cognition, depression, anxiety) trajectory after surgery.

Conditions

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Pain, Postoperative

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
This will be a single-center, quadruple-blinded, pilot randomized controlled trial at the University of Michigan Health System.

Study Groups

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Experimental

Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group.

Group Type EXPERIMENTAL

Caffeine Citrate

Intervention Type DRUG

Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.

Control

Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group.

Group Type PLACEBO_COMPARATOR

Dextrose Water

Intervention Type DRUG

Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.

Interventions

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Caffeine Citrate

Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.

Intervention Type DRUG

Dextrose Water

Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Adult (\>/= 18 years old) undergoing non-cardiac, non-neurologic, non-major vascular surgery requiring general anesthesia

Exclusion Criteria

* Emergency surgery
* Cognitive impairment precluding capacity for informed consent
* Uncontrolled cardiac arrhythmias
* Seizure disorders
* Preoperative opioid use
* Diabetes
* Liver failure
* Pregnancy
* Breastfeeding
* Severe visual or auditory impairment (may hinder cognitive function testing)
* Patients unable to speak English.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Michigan

OTHER

Sponsor Role lead

Responsible Party

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Phillip Vlisides

Assistant Professor of Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Phillip Vlisides, MD

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor of Anesthesiology

Locations

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Michigan Medicine

Ann Arbor, Michigan, United States

Site Status

Countries

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United States

References

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Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30.

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Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 28403427 (View on PubMed)

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Nelson AM, Battersby AS, Baghdoyan HA, Lydic R. Opioid-induced decreases in rat brain adenosine levels are reversed by inhibiting adenosine deaminase. Anesthesiology. 2009 Dec;111(6):1327-33. doi: 10.1097/ALN.0b013e3181bdf894.

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Gauthier EA, Guzick SE, Brummett CM, Baghdoyan HA, Lydic R. Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of Sprague Dawley rat. Anesthesiology. 2011 Oct;115(4):743-53. doi: 10.1097/ALN.0b013e31822e9f85.

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Vlisides PE, Li D, McKinney A, Brooks J, Leis AM, Mentz G, Tsodikov A, Zierau M, Ragheb J, Clauw DJ, Avidan MS, Vanini G, Mashour GA. The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial. Anesth Analg. 2021 Jul 1;133(1):233-242. doi: 10.1213/ANE.0000000000005532.

Reference Type BACKGROUND
PMID: 33939649 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HUM00135919

Identifier Type: -

Identifier Source: org_study_id

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