Stellate Ganglion Blockade in Post-Menopausal Women — R01  

Hot Flashes Clinical Trial

Official title: Stellate Ganglion Blockade for the Management of Vasomotor Symptoms

Status Suspended

Clinical Trial Summary

Hot flashes and night sweats (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 160 postmenopausal women with 50 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.

Clinical Trial Description

Scope:

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

Specific Goals and Objectives:

Primary Objective

1. To determine the effect of SGB for reducing frequency and intensity of menopausal VMS.

Hypothesis 1a. Seven-day mean frequency of VMS will be lower in women randomized to active SGB compared to sham control.

Hypothesis 1b. Seven-day mean intensity of VMS will be lower in women randomized to active SGB compared to sham control.

Hypothesis 1c. The VMS Intensity (Frequency*Severity), will be lower in women randomized to active SGB compared to sham control.

Secondary Objectives

2. To evaluate the effect of SGB on VMS Intensity, 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.

3. To probe the mechanisms by which SGB improves VMS.

Hypothesis 3a. In a nested sub study, 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 as measured by skin sympathetic nerve monitoring (SKNA) and these effects will be reassessed at 2 and 4 weeks after the intervention to assess if effects of SGB on stellate ganglion activity are long lasting. ;

Related Conditions & MeSH terms

• Hot Flashes
• Hot Flushes
• Vasomotor Symptoms

• NCT number: NCT02907983
• Study type: Interventional
• Source: Northwestern University
• Status: Suspended
• Phase: Phase 2
• Start date: July 10, 2018
• Completion date: August 31, 2026