Vasomotor Symptoms and Cardiovascular Control

Vasomotor Symptoms Clinical Trial

Official title: Vasomotor Symptoms and Cardiovascular Control

Status Withdrawn

Clinical Trial Summary

The purpose of this study is to preliminarily determine whether the frequency and/or severity of vasomotor symptoms (VMS) at baseline, and then after symptom reduction with gabapentin, relates to various cardiovascular control measures.

Clinical Trial Description

Visit 1: Screening & Acclimation Visit

The informed consent process for the study will be completed and a signed informed consent form will be obtained at Spaulding Hospital Cambridge. Subjects will be screened to ensure they meet preliminary eligibility criteria. All subjects will undergo a clinical interview to determine the presence of any medical disorders. The following study assessments will be completed:

• 12-lead EKG

• Resting blood pressure and heart rate

• Height and Weight

Visit 2: VMS Determination and At-Home Assessments Subjects will be interviewed about their mental health history, and will complete questionnaires about their VMS, related quality-of-life symptoms (sleep, mood) and quality-of-life. Blood will be drawn to confirm eligibility and to assess for diabetes and chronic kidney disease (see exclusion criteria). Subjects will be given a 7-day VMS Diary and a 7-day Sleep Diary at the end of this visit, to be completed at home during the following week. Participants will also be given an actigraphic watch to take home to wear for 7 days in order to capture sleep/wake patterns and activity levels for exploratory analyses. During the 7 days of at-home VMS and sleep monitoring, subjects will also wear a portable VMS monitor for 24 hours to measure objective VMS frequency.

Visit 3: Final Eligibility Determination & Lab VMS Monitoring Subjects will return the objective VMS monitor and the VMS and sleep diaries, and the results of their blood tests taken during the Visit 2 will be reviewed to ensure eligibility. Eligible subjects will participate in a 6-hour laboratory objective VMS monitoring session by wearing an objective VMS monitor while simultaneously subjectively monitoring VMS experienced with a written diary and an event marker. Objective VMS measures obtained during this visit will be the primary baseline measure of VMS for investigation. Those who have at least 2 objective VMS measured during the 6-hour monitoring period will be deemed eligible and referred for baseline studies and to start medication. Participants will be given additional VMS and sleep diaries to complete on a daily basis throughout the rest of the study period.

Visit 4: Laboratory Testing Visit & Medication Distribution All studies will be performed between ~8-10 am and will occur at the same time for the second laboratory testing visit. All subjects will be instructed to abstain from vigorous exercise for 2 days prior to each study to avoid autonomic and neuroendocrine effects of exercise. In addition, subjects will refrain from caffeine and alcohol for the previous 24 hrs, and be studied after a 12 hr fast.

A. Study Visit: Parameters to be Measured

1. Electrocardiogram.

2. Arterial Pressure.

3. Respiration.

4. Sympathetic Microneurography.

5. Beat-by-Beat Leg Blood Flow. B. Drugs to Study Human Physiology

1) Intravenous bolus injection of 100 ug nitroprusside bolus (a vasodilator which drops pressure) 2) Intravenous bolus injection 150 ug phenylephrine bolus (a vasoconstrictor which raises pressure).

These two drugs are used to drop and raise pressure through a range of arterial pressures within a very short time, approximately 2 minutes.

These medications raise and lower blood pressure by the same amount typically experienced during the day when performing activities such as climbing stairs or moving from sitting to standing.

C. Data to be collected/Timing of collection The study visit will take about 4 hours. Throughout the protocol, subjects will lie supine and will be instrumented for measurement of the ECG, beat-by-beat arterial pressure, brachial arterial pressure, respiratory excursions, and popliteal blood flow velocity. After instrumentation and calibration, instrumentation for measurement of peroneal nerve muscle sympathetic activity will commence, with the internal search lasting a maximum of 60 minutes.

After either successful or unsuccessful procurement of the nerve recording, the testing protocol will start:

Testing Protocol

1. Baseline recordings/measurement (~10 minutes): Subjects will rest quietly for 10 minutes.

2. Modified Oxford Baroreflex tests (5 minutes/trial, 2 trials, ~30 minutes total): An intravenous bolus injection of 100 ug nitroprusside bolus, followed in 1 minute by a 150 ug phenylephrine bolus. After the first trial, a second modified Oxford baroreflex test will be performed. At least 10-15 minutes will be allowed between the baroreflex trials to insure that heart rate, blood pressure and nerve activity return to resting levels. Subjects will be continually assessed for adverse events and symptoms related to hypotension.

3. Sustained isometric handgrip exercise (~10 minutes): Subjects will be asked to perform an isometric handgrip exercise at 30% of maximum effort sustained to fatigue.

4. Valsalva's maneuver (~5 minutes): Subjects will be asked to blow into a tube via a mouthpiece and generate a pressure of ~40 mmHg sustained for 12 seconds. Data will be collected for one minute prior to the maneuver, one minute after, with two minutes of recovery between trials. This will be repeated to obtain three successful trials.

5. Paced breathing (~15 minutes total): Subjects will be asked to maintain a constant breathing frequency of 15 breaths/min (0.25 Hz) following an audio signal (i.e., "in, two, out, two") for 5 minutes after a short period of acclimation.

Distribution of Study Medication: After all baseline measures are complete, study medication (gabapentin) will be distributed to all study participants and participants will be instructed as to how to take and titrate the medication dose.

Visit 5a: Medication Dosage & Adverse Event Monitoring (Telephone) Study staff will check in with study participants over the telephone after they have been on gabapentin for approximately one week to monitor any side effects or adverse events of the medication. If subjects are experiencing intolerable side effects, they will be taken off of the medication while completing the remaining study procedures. In order to track potential after effects of microneurography, subjects who had the electrode placed beneath the surface of their skin will be given the Microneurography Questionnaire (MSNA). Over the last 18 years of performing the technique, roughly 5% of participants have after effects, and of these the most often reported effect (>90%) is slight bruising at the site of insertion.

Visit 5b: Medication Dosage & Adverse Event Monitoring (Telephone) Study staff will check in with study participants over the telephone after they have been on gabapentin for approximately three weeks to monitor any side effects or adverse events of the medication. If subjects are experiencing intolerable side effects, they will be taken off of the medication while completing the remaining study procedures.

Visit 6: Objective VMS Monitoring All subjects will repeat the 6-hour laboratory objective VMS monitoring session on gabapentin for post-treatment measures of VMS, as described above for Visit 3. Participants will also complete the same set of pre-treatment questionnaires about their VMS, related quality-of-life symptoms (sleep, mood) and quality-of-life. All subjects will be given the ambulatory VMS monitor to wear for 24 hours at home, to capture the frequency of VMS in the ambulatory setting as well as the actigraphic watch to wear for a one-week period. Participants will be reminded to continue to complete their VMS and sleep diaries.

Visit 7: Laboratory Testing Visit & Medication Collection Procedures performed during Visit 4 will be repeated at Visit 7, to collect data on cardiovascular measures after participants have been on gabapentin for at least 4 weeks at the full dose. All VMS and sleep diaries, as well as unused study medication, actigraphic watch, and the objective VMS monitor, will be returned and collected at this visit. ;

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Health
• Vasomotor Symptoms

• NCT number: NCT02202707
• Study type: Interventional
• Source: Beth Israel Deaconess Medical Center
• Status: Withdrawn
• Phase: N/A
• Start date: May 2014
• Completion date: June 2016