Sevoflurane for Neurocognitive Effects Related to Pain and Anesthesia
(SENS Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Keith M. Vogt, MD, PhD
Must not be taking: Antidepressants, Antipsychotics, Antiepileptics, others
Disqualifiers: Pregnancy, Chronic pain, Neurologic, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to determine the effects of acute pain on long-term memory and conditioned physiologic responses in the presence and absence of low dose sevoflurane. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena. The study will occur over 2 visits and involves no long-term follow up.
Will I have to stop taking my current medications?
Yes, you may need to stop taking certain medications. The trial excludes people who regularly take medications like antidepressants, anti-anxiety drugs, and some others. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment Sevoflurane for Neurocognitive Effects Related to Pain and Anesthesia?
Research shows that peripheral nerve stimulation (PNS) is effective for managing chronic pain and has potential for reducing postoperative pain and opioid use. This suggests that PNS, as part of the treatment, may help in managing pain related to anesthesia.
12345Is peripheral nerve stimulation (PNS) generally safe for humans?
Peripheral nerve stimulation (PNS) has been used since 1965 for pain management and is generally considered safe, with adverse events being mostly minor. It avoids risks associated with spinal cord stimulation, such as central cord injury.
12678How does the drug sevoflurane differ from other treatments for neurocognitive effects related to pain and anesthesia?
Sevoflurane is unique because it targets hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which may play a role in neuroinflammation associated with anesthesia. Unlike other anesthetics, sevoflurane has been shown to have both neuroprotective and neuroinflammatory effects, depending on the context, and its impact on nerve growth factor (NGF) pathways is a novel area of study.
910111213Eligibility Criteria
This trial is for healthy adults aged 18-59 with normal hearing, memory, and body weight. Participants must be native English speakers with at least a high school education, not pregnant, without chronic diseases or severe medical conditions like heart disease or seizures, and free from drug use including marijuana and heavy alcohol consumption.Inclusion Criteria
Have none of the specific exclusion criteria
I have a working email and phone number.
Anticipate ability to participate in all visits required for the phase of the study in which they are enrolled
+4 more
Exclusion Criteria
You are afraid of being in small, enclosed spaces.
You have had a bad reaction to anesthesia in the past.
You drink alcohol every day or drink a lot of alcohol. You have a history of drinking too much alcohol.
+21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Baseline Assessment
Participants undergo baseline functional MRI scans without sevoflurane to assess brain activity during pain and memory tasks
1 day
1 visit (in-person)
Treatment
Participants receive sevoflurane and undergo functional MRI scans to assess the effects on pain processing and memory encoding
1 day
1 visit (in-person)
Follow-up
Participants are monitored for memory performance 24 hours post-learning experiment
1 day
1 visit (in-person)
Participant Groups
The study tests how acute pain affects long-term memory and physiological responses with/without low-dose sevoflurane anesthesia. It involves two visits with no long-term follow-up using functional MRI to examine brain activity related to these effects.
1Treatment groups
Experimental Treatment
Group I: Sevoflurane+PainExperimental Treatment2 Interventions
Single-arm study. All subjects receive sevoflurane and painful electric nerve stimulation, as described in the interventions.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PittsburghPittsburgh, PA
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Who Is Running the Clinical Trial?
Keith M. Vogt, MD, PhDLead Sponsor
Keith M VogtLead Sponsor
National Institute of General Medical Sciences (NIGMS)Collaborator
References
Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation: A Pragmatic Effectiveness Trial of a Nonpharmacologic Alternative for the Treatment of Postoperative Pain. [2021]Percutaneous peripheral nerve stimulation (PNS) is an analgesic modality involving the insertion of a lead through an introducer needle followed by the delivery of electric current after needle withdrawal. This modality has been used extensively to treat chronic pain, but only small series have been published involving postoperative pain. The ultimate objective of this study is to determine the postoperative effects of percutaneous PNS following moderately to severely painful ambulatory surgery within a real-world clinical practice setting. The primary hypothesis is that surgical pain and opioid consumption during the initial 7 days after surgery will be reduced by percutaneous PNS compared with usual and customary analgesia (dual primary outcome measures).
Acute postoperative pain management with percutaneous peripheral nerve stimulation: the SPRINT neuromodulation system. [2022]Ultrasound-guided percutaneous peripheral nerve stimulation (PNS) may be used to treat acute postoperative pain for various types of surgeries. This modality avoids several limitations of traditional local anesthetic-based peripheral nerve blocks including avoidance of motor blockade and sensory deficits.
Evidence-Based Clinical Guidelines from the American Society of Pain and Neuroscience for the Use of Implantable Peripheral Nerve Stimulation in the Treatment of Chronic Pain. [2022]The objective of this peripheral nerve stimulation consensus guideline is to add to the current family of consensus practice guidelines and incorporate a systematic review process. The published literature was searched from relevant electronic databases, including PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from database inception to March 29, 2021. Inclusion criteria encompassed studies that described peripheral nerve stimulation in patients in terms of clinical outcomes for various pain conditions, physiological mechanism of action, surgical technique, technique of placement, and adverse events. Twenty randomized controlled trials and 33 prospective observational studies were included in the systematic review process. There is Level I evidence supporting the efficacy of PNS for treatment of chronic migraine headaches via occipital nerve stimulation; chronic hemiplegic shoulder pain via stimulation of nerves innervating the trapezius, supraspinatus, and deltoid muscles; failed back surgery syndrome via subcutaneous peripheral field stimulation; and lower extremity neuropathic and lower extremity post-amputation pain. Evidence from current Level I studies combined with newer technologies facilitating less invasive and easier electrode placement make peripheral nerve stimulation an attractive alternative for managing patients with complex pain disorders. Peripheral nerve stimulation should be used judiciously as an adjunct for chronic and acute postoperative pain following adequate patient screening and positive diagnostic nerve block or stimulation trial.
Educational Curriculum for Peripheral Nerve Stimulation Developed by the North American Neuromodulation Society. [2023]Peripheral nerve stimulation (PNS) is an effective neuromodulation therapy for chronic neuropathic and nociceptive pain. Although the total number of PNS implantations has increased over the last decade, no curriculum exists to guide training and learning of this therapy. The goal of the North American Neuromodulation Society (NANS) education committee is to develop a series of competency-based curriculums for neuromodulation therapies. The PNS curriculum is the latest part of such series, following the curriculums for spinal cord stimulation and intrathecal drug delivery system.
Percutaneous Peripheral Nerve Stimulation (Neuromodulation) for Postoperative Pain: A Randomized, Sham-controlled Pilot Study. [2022]Percutaneous peripheral nerve stimulation is an analgesic technique involving the percutaneous implantation of a lead followed by the delivery of electric current using an external pulse generator. Percutaneous peripheral nerve stimulation has been used extensively for chronic pain, but only uncontrolled series have been published for acute postoperative pain. The current multicenter study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent clinical trial and (2) estimate the treatment effect of percutaneous peripheral nerve stimulation on postoperative pain and opioid consumption.
Long-term peripheral nerve stimulation for painful nerve injuries. [2019]Although peripheral nerve stimulation (PNS) has been used in the treatment of pain since 1965, only a few follow-up studies have been published. The aim of the present retrospective study was to carefully assess the long-term efficacy and safety of PNS in the treatment of painful nerve injuries.
Peripheral Nerve Stimulation for Chronic Pain: A Systematic Review of Effectiveness and Safety. [2023]Peripheral nerve stimulation (PNS) was the first application of neuromodulation. Widespread application of PNS was limited by technical concerns. Recent advances now allow the percutaneous placement of leads with ultrasound or fluoroscopic guidance, while the transcutaneous powering of these leads removes the need for leads to cross major joints. This systematic review was written to assess the current status of high-quality evidence supporting the use of PNS for pain conditions treated by interventional pain physicians. The available literature on PNS, limited to conditions treated by interventional pain physicians, was reviewed and the quality assessed. Literature from 1966 to June 2021 was reviewed. The outcome measures were pain relief and functional improvement. One hundred and two studies were identified. Five randomized controlled trials (RCT) and four observational studies, all case series, met the inclusion criteria. One RCT was of high quality and four were of moderate quality; all four case series were of moderate quality. Three of the RCTs and all four case series evaluated peripheral nerve neuropathic pain. Based upon these studies, there is level II evidence supporting the use of PNS to treat refractory peripheral nerve injury. One moderate-quality RCT evaluated tibial nerve stimulation for pelvic pain, providing level III evidence for this indication. One moderate-quality RCT evaluated surgically placed cylindrical leads for cluster headaches, providing level III evidence for this indication. The evidence suggests that approximately two-thirds of patients with peripheral neuropathic pain will have at least 50% sustained pain relief. Adverse events from PNS are generally minor. A major advantage of PNS over spinal cord stimulation is the absence of any risk of central cord injury. The study was limited by the paucity of literature for some indications. No studies dealt with joint-related osteoarthritic pain.
Feasibility of ultrasound-guided percutaneous placement of peripheral nerve stimulation electrodes and anchoring during simulated movement: part two, upper extremity. [2019]Peripheral nerve stimulation (PNS) may provide analgesia for neuropathic pain syndromes in that nerve distribution. PNS electrode placement using ultrasound (US) guidance for upper extremity pain syndromes has not been reported. Existing anchoring technology may allow permanent implantation without significant migration.
PEX5R/Trip8b-HCN2 channel regulating neuroinflammation involved in perioperative neurocognitive disorders. [2022]Clinical and animal studies demonstrated that neuroinflammation from anesthesia (sevoflurane) is the main contributor to cause perioperative neurocognitive disorders (PND). Recently, it was reported that microglia respond to hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which was the target of sevoflurane. Whether HCN channels are involved in the induction of neuroinflammation after sevoflurane exposure is still unclear.
Effect of Anesthetic Agents on Cognitive Function and Peripheral Inflammatory Biomarkers in Young Patients Undergoing Surgery for Spine Disorders. [2022]Exposure to anesthesia has been postulated to affect the cognitive function by inciting central nervous system inflammation. Hence, we planned to compare the psychometrical effects of anesthetic agents propofol, desflurane, or sevoflurane on postoperative cognitive function and also measure the change in concentration of serum S-100β, interleukin (IL)-6, and tumor necrosis factor (TNF)-α to look for the contribution of systemic inflammation.
Neuroprotective potential of sevoflurane against isoflurane induced cognitive dysfunction in rats via anti-inflammatory and antioxidant effect. [2023]Intravenous anesthetics have excellent analgesic activity without inducing the side effect in the respiratory system. The aim and objective of the current experimental study was to access the neuroprotective effect of sevoflurane against isoflurane induced cognitive dysfunction in rats.
Influence of Different Sevoflurane Concentrations on Postoperative Cognitive Function in Aged Rats. [2023]Postoperative cognitive dysfunction may be associated with neuroinflammation, and sevoflurane suppresses surgery-induced inflammation. We hypothesized that low concentrations of sevoflurane would result in more impaired postoperative cognitive function compared to high concentrations.
Nerve growth factor metabolic dysfunction contributes to sevoflurane-induced cholinergic degeneration and cognitive impairments. [2020]General anesthesia with sevoflurane is associated with an increased incidence of postoperative cognitive dysfunction. Previous studies have shown that sevoflurane anesthesia can affect the integrity and function of basal forebrain cholinergic neurons (BFCNs) which are essential for learning and memory. However, the underlying mechanisms remain largely unknown. Here, we demonstrated that exposure to 2.5% sevoflurane induced significant loss of BFCNs and caused impairments of the spatial and the fear memory. Further, sevoflurane exposure significantly reduced the level of nerve growth factor (NGF), an important factor for the survival and phenotype maintenance of BFCNs, by disrupting its synthesis pathways in the brain. More importantly, NGF administration not only prevented the loss of BFCNs but also ameliorated the cognitive impairments in sevoflurane-treated mice. Our findings indicate that NGF metabolic dysfunction contributes to sevoflurane-associated BFCNs degeneration and subsequent cognitive deficits.