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Stellate Ganglion Blockade in Post-Menopausal Women (R01)

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ClinicalTrials.gov Identifier: NCT02907983
Recruitment Status : Not yet recruiting
First Posted : September 20, 2016
Last Update Posted : March 15, 2018
Sponsor:
Collaborators:
University of Illinois at Chicago
Indiana University
Information provided by (Responsible Party):
David Walega, Northwestern University

Brief Summary:

Hot flashes and night sweats (i.e., vasomotor symptoms, VMS) affect 80% of women during the menopausal transition (MT). VMS are associated with decreased quality of life, increased depressive and anxiety symptoms, memory complaints, sleep disturbance, and reduced work productivity. Hormone therapy (HT) is highly effective in reducing VMS, but the use of HT declined 75% to 80% in the U.S. after the Women's Health Initiative (WHI) raised safety concerns about HT. In 2013, the Food and Drug Administration (FDA) approved paroxetine, a selective serotonin reuptake inhibitor (SSRI; 7.5 mg), as the first non-hormonal treatment for VMS. SSRIs are an important treatment option for many women, but their use in treating VMS is limited by lower effectiveness when compared to HT, side effects, and relapse of symptoms following treatment discontinuation. Identifying safe and effective non-hormonal treatments for VMS remains a priority in women's health research.

Stellate ganglion blockade (SGB), used for decades in pain management, is a potential new approach to VMS treatment. Located in the cervical spine region, the stellate ganglia are part of the sympathetic nervous system. Although SGB is commonly performed to treat neuropathic pain, hyperhidrosis or vascular insufficiency, anatomic studies reveal connections between this ganglion and thermoregulatory regions of the brain, specifically the insular cortex.

In this clinical trial, we aim to assess whether stellate ganglion block (SGB) with bupivacaine, a local anesthetic, is an effective and safe non-hormonal intervention for women seeking relief from vasomotor symptoms (VMS), and identify the physiologic mechanisms underlying SGB effects. Outcomes will include frequency and intensity of hot flashes, objectively-measured VMS, mood, quality of life, sleep, and memory performance in 220 postmenopausal women with 28 or more moderate to very severe hot flashes per week as measured by self-report for six months. They will be reassessed at 3 and 6 months following the SGB or a sham intervention for objective hot flashes and quality of life measures. Mechanistic outcomes (neuroimaging) will be obtained at baseline and 3 months following the intervention. Ambulatory monitoring of sympathetic nervous system function (SKNA) will be performed at baseline before the procedure, during the procedure and 1 hour following the procedure. This will be repeated at 2 and four weeks following the SGB or sham procedure for 1 hour recordings.


Condition or disease Intervention/treatment Phase
Hot Flashes Hot Flushes Vasomotor Symptoms Drug: Stellate Ganglion Block Injection with Bupivicaine Drug: Saline injection Phase 2

Detailed Description:

Scope:

Post-menopausal women with moderate to very severe VMS will be enrolled as participants in this study.

Hypotheses:

We predict that compared to sham intervention, SGB will reduce the frequency of VMS, improve mood and anxiety, increase quality of life, and improve memory, normalize brain activity in thermoregulatory brain areas and reduce efferent sympathetic nerve activity but have no effect on sleep or other cognitive functions. By providing a more definitive understanding of the effectiveness of SGB, possible secondary benefits, and mechanisms of action, these findings will fill a critical gap in treatment options available to women.

Specific Goals and Objectives:

Aim 1: To determine the effect of SGB for reducing menopausal VMS. Hypothesis 1: The frequency and intensity of VMS will be lower in women randomized to active SGB compared to sham control.

Aim 2: To evaluate the effect of SGB on objective VMS, mood, memory, and sleep quality.

Hypothesis 2a: The frequency of objectively measured VMS will be lower in women randomized to active SGB compared to sham control.

Hypothesis 2b: Depressive symptoms and memory, but not sleep quality, will improve more in women randomized to active SGB compared to sham control. Hypothesis 2c: The magnitude of improvements in memory will relate to the magnitude of reduction in VMS, even after controlling for sleep.

Aim 3: To probe the mechanisms by which SGB improves VMS. Hypothesis 3a: In a nested substudy, neuroimaging assessments will reveal that compared to sham control, active SGB is associated with a) decreased functional connectivity in the default mode network during the resting state, particularly for networks supporting the insula and hippocampus; b) reduced activation in the hippocampus, dorsolateral prefrontal cortex, and anterior cingulate during a verbal memory task; and c) reduced activation in the amygdala during an emotion processing task.

Hypothesis 3b: Compared to sham control, SGB will immediately diminish ipsilateral stellate ganglion nerve activity and sympathetic tone.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Care Provider)
Primary Purpose: Supportive Care
Official Title: Stellate Ganglion Blockade for the Management of Vasomotor Symptoms
Estimated Study Start Date : May 1, 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Menopause
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Bupivicaine
Stellate Ganglion Block injection with bupivicaine
Drug: Stellate Ganglion Block Injection with Bupivicaine
A computer-generated stratified randomization scheme by self-reported race and by etiology of menopause (natural versus surgical menopause) will be used to assign participants to receive either a SGB with bupivacaine or a sham injection with saline. Randomization will be performed by the injectionist immediately before the injection procedure by opening an opaque envelope to reveal the participant number and group assignment printed on an index card.
Other Name: Marcaine
Sham Comparator: Saline
Saline injection
Drug: Saline injection
A computer-generated stratified randomization scheme by self-reported race and by etiology of menopause (natural versus surgical menopause) will be used to assign participants to receive either a SGB with bupivacaine or a sham injection with saline. Randomization will be performed by the injectionist immediately before the injection procedure by opening an opaque envelope to reveal the participant number and group assignment printed on an index card.
Other Name: Sodium chloride solution



Primary Outcome Measures :
  1. Changes from baseline and intensity of subjective hot flashes (HF) [ Time Frame: Up to 24 weeks (6 months) following intervention ]
    Changes from baseline of paper diary (subjective) measures of frequency and intensity


Secondary Outcome Measures :
  1. Changes from baseline of frequency of objective hot flashes [ Time Frame: Up to 24 weeks (6 months) following intervention ]
    Changes from baseline frequency of objective HFs over a 24 hour period using a validated skin conductance monitor at baseline, 12 weeks (3 months) and 24 weeks (6 months)

  2. Composite changes from baseline of scores of neurocognitive measures [ Time Frame: Up to 24 weeks (6 months) following intervention ]
    Composite changes from baseline of scores to include:California Verbal Learning Test (CVLT) List A, List B, Short-Delay Free Recall, Short-Delay Cued Recall, Long Delay Free Recall, Long Delay Cued Recall, Card Rotation Tests, Digit Span (Forward and Backward), Finding As, Letter, Semantic and Phonemic Fluency, Logical Memory Subtest of Wechsler Memory Scale (WMS-R/LM-R) Part 1 and (WMS-R/LM-R) Part 2, Mini-Mental State Exam (MMSE), Memory Functioning Questionnaire (MFQ),Closing Question at baseline, 12 weeks (3 months) and 24 weeks (6 months)

  3. Composite changes from baseline of scores of measures of mood [ Time Frame: Up to 24 weeks (6 months) following intervention ]
    Composite changes from baseline of scores of mood to include:Beck Depression Inventory II (BDI), Beck Anxiety Inventory (BAI) and Center for Epidemiological Studies-Depression (CES-D) at baseline, 12 weeks (3 months) and 24 weeks (6 months)

  4. Composite changes from baseline of scores of measures of quality of life [ Time Frame: Up to 24 weeks (6 months) following intervention ]
    Composite changes from baseline of scores of quality of life measures to include:Female Sexual Distress Scale (FSDS-R), Menopause Quality of Life Questionnaire (MENQUAL), Patient Global Impression of Change (PGIC), Utian Quality of Life Scale (UQOL), Hot Flash Related Daily Interference Scale (HFRDIS), PAIN Intensity and Interference Scale (PEG) Post Injection Questionnaire at baseline, 12 weeks (3 months) and 24 weeks (6 months)

  5. Changes from baseline of scores of measures of sleep [ Time Frame: Up to 24 weeks (6 months) following intervention ]
    Composite changes from baseline of scores of Pittsburgh Sleep Quality Inventory (PSQI) at baseline, 12 weeks (3 months) and 24 weeks (6 months)

  6. Changes from baseline of actigraph measures of sleep [ Time Frame: Up to 24 weeks (6 months) following intervention ]
    Changes from baseline of actigraph changes in sleep at baseline, 12 weeks (3 months) and 24 weeks (6 months)

  7. Changes from baseline of Skin Sympathetic Nerve Activity (SKNA) [ Time Frame: Up to 2 and 4 weeks following intervention ]
    Changes of recordings of SKNA using an FDA-approved, specially-configured portable device (Biomation ME6000) in a subset of 60 participants

  8. Changes from baseline of Functional MRI [ Time Frame: Up to 12 weeks following intervention ]
    Changes in fmri activity in a subset of 60 participants at baseline and 3 months following the intervention



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. aged 40 to 70 years; for cognition testing, upper age limit is 62
  2. 28 or more reported moderate-to-very severe hot flashes per week
  3. a minimum of two weeks of VMS diary recording prior to SGB
  4. willingness to undergo fluoroscopy-guided SGB or sham treatment.

Exclusion Criteria:

  1. conditions that preclude SGB or sham intervention (e.g., anatomic abnormalities of the anterior neck or cervical spine ; goiter, cardiac/pulmonary compromise; acute illness/infection; coagulopathy or bleeding disorder; allergic reactions/contraindications to a local anesthetic or contrast dye, uncontrolled hypertension defined as systolic BP >190 mm Hg and diastolic BP >100 mm Hg
  2. FSH< 50 ml U/ml,
  3. use of treatments in the two prior months that can affect VMS frequency or severity, including oral or transdermal hormone therapy, botanicals (e.g., soy, red clover, black cohosh, etc.), oral contraceptives, serotonin selective reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), gabapentin, pregabalin, clonidine, selective estrogen receptor modulators, aromatase inhibitors, tissue selective estrogen complexes;
  4. For cognition testing: conditions or disorders that can affect performance on cognitive tests (e.g., dementia/mild cognitive impairment, Mini-Mental State Exam (MMSE) greater than or equal to 27); stroke; traumatic brain injury; alcohol/substance use; inability to write, speak, or read in English, English as a second language, participation in other studies involving tests of cognitive abilities
  5. conditions that can affect depressive symptoms (e.g., current diagnosis of major depression, bipolar disorder, or other Axis I Psychiatric disorder); Beck Depression Inventory (BDI) > 30
  6. Exclusion criteria for neuroimaging study: implantable pulse generators for pacemakers, defibrillator devices and most but not all spinal cord stimulators or deep brain stimulator, ferrous-containing metals within the body (e.g., braces, aneurysm clips, shrapnel/retained particles)inability to tolerate small, enclosed spaces without anxiety(e.g. claustrophobia), weight > 300 lbs. unless height is sufficiently high [e.g., + 5'11"] so that waist and shoulder circumference do not prevent her from fitting in the scanner;
  7. Exclusion criteria for SKNA study only allergic to adhesive in electrode

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02907983


Contacts
Contact: Suzanne Banuvar, MPA,CCRC 312-695-7771 s-banuvar@northwestern.edu

Locations
United States, Illinois
Anesthesiology Pain Medicine Center
Chicago, Illinois, United States, 60605
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
David Walega
University of Illinois at Chicago
Indiana University
Investigators
Principal Investigator: David R. Walega, MD, MSCI Northwestern University

Responsible Party: David Walega, Principal Investigator, Northwestern University
ClinicalTrials.gov Identifier: NCT02907983     History of Changes
Other Study ID Numbers: STU00203490
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by David Walega, Northwestern University:
Menopause
Post-menopausal

Additional relevant MeSH terms:
Hot Flashes
Signs and Symptoms
Bupivacaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents