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Diaphragmatic Breathing and Heart Rate Variability Training for Improving Hypertension in Fragile X Associated Tremor/Ataxia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03816540
Recruitment Status : Recruiting
First Posted : January 25, 2019
Last Update Posted : January 25, 2019
UC Davis MIND Institute
UC Davis, Mini-Grant Geriatrics
Information provided by (Responsible Party):
University of California, Davis

Brief Summary:

To study whether heart rate variability training and respiratory coherence can improve hypertension in individuals with FXTAS.

All patients will receive HRV biofeedback training for 20 sessions. Our hypothesis is that individuals with FXTAS who undergo 20 sessions of biofeedback training will improve self-regulatory skills for reducing hypertension, as measured by blood pressure measurement to below 140/90. The investigators hypothesize that individuals who successfully develop increased heart rate variability and better synchrony between heart rhythm and respiration will show the greatest improvements in self-regulatory skills for hypertension.

Condition or disease Intervention/treatment Phase
Hypertension FXTAS Device: HRV and respiratory coherence biofeedback Phase 3

Detailed Description:

Fragile X-associated tremor ataxia syndrome (FXTAS) is a late onset neurodegenerative disease that affects carriers of the fragile X premutation. This project proposes the evaluation of an innovative intervention program that promotes self-regulatory skills for hypertension in individuals with FXTAS. Using a control-group experimental design, the investigators propose to explore the efficacy of a biofeedback treatment to support self-regulatory processes on the physiological level: Heart Rate Variability (HRV) and respiratory coherence biofeedback.

Chronic hypertension contributes to cardiovascular complications, dementia, and increased risk of stroke. Our results indicate that the risk of hypertension is significantly elevated in male premutation carriers with FXTAS compared with carriers without FXTAS and controls.

Several research studies showed high levels of physiological arousal in individuals with Fragile X-Associated Disorders (FXS/FX-AD), related to a dysregulation of the sympathetic and parasympathetic nervous system. One parameter to measure physiological arousal is cardiovascular activity. It provides an index of parasympathetic and sympathetic involvement of the autonomic nervous system. Heart rate is under the control of efferent sympathetic and vagal activities directed to the sinus node, which are modulated by central brain stem (vasomotor and respiratory centers) and peripheral oscillators (oscillation in arterial pressure and respiratory movements). Spectral analysis of heart rate variability (HRV) is a reliable quantitative method for analyzing the modulatory effects of neural mechanisms on the sinus node.

Biofeedback treatments are reported for over 30 years. Biofeedback provides specific information about internal biological processes (i.e. muscle activity, respiration, heart rate variability, skin temperature and brain electrical activity) in an individual. In general, by enhancing the awareness of these processes and training to volitional control over them, specific parameters can be improved. The internal biological processes can be measured with a specific biofeedback equipment that convert this data into signals, often in the form of auditory, visual or somatosensory events, so that the individual can perceive real-time changes in their physiological activity. As the individual learns to control these events, healthier physiological processes are conditioned. Depending upon the physiological processes targeted, healthier patterns of activity can be achieved by most people after they have participated in 10 to 50 sessions of biofeedback supported with professional coaching and practice. Various biofeedback protocols and assistive electronic technologies such as the NeXus-10, emWave Personal Stress Reliever® or StressEraser® exist to enhance the balance of parasympathetic activity, vagal tone, increase HRV and synchronize respiration with the heart rhythm (i.e., the slowing down and speeding up of the heart over time).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Same intervention will be applied to FXTAS-affected and unaffected (comparison) participants.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Diaphragmatic Breathing and Heart Rate Variability Training for Improving Hypertension in Fragile X Associated Tremor/Ataxia
Actual Study Start Date : May 1, 2018
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019

Arm Intervention/treatment
Experimental: FXTAS-affected
FXTAS-affected participants will receive HRV and respiratory coherence biofeedback training for 20 sessions.
Device: HRV and respiratory coherence biofeedback
Biofeedback treatment to support self-regulatory processes on the physiological level: heart rate variability (HRV) and respiratory coherence.

Active Comparator: FXTAS-unaffected
FXTAS-unaffected participants will be assessed to compare the effects of biofeedback based on FXTAS status. This arm will receive HRV and respiratory coherence biofeedback training for 20 sessions.
Device: HRV and respiratory coherence biofeedback
Biofeedback treatment to support self-regulatory processes on the physiological level: heart rate variability (HRV) and respiratory coherence.

Primary Outcome Measures :
  1. Change in blood pressure (systolic & diastolic) [ Time Frame: Baseline, 4 to 6 weeks ]
    Blood pressure is measured at the brachial artery of left arm using an electronic blood pressure monitor with an inflatable cuff, repeated three times at each site, and averaged. Less than 120/80 mmHg is considered "normal," 120/80 to 139/89 mmHg is "prehypertension," and above 140/90 mmHg is "hypertension."

  2. Clinical Global Impression Scale - Severity (CGI-S) [ Time Frame: Baseline ]
    The CGI-Severity (CGI-S) will be assessed at baseline according to the severity of hypertension, which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline elevated; 3=mildly elevated; 4=moderately elevated; 5=markedly elevated; 6=severely elevated; 7= extremely elevated. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. Symptoms and behavior can fluctuate over a week; the score should reflect the average severity level across the seven days.

  3. Clinical Global Impression Scale - Improvement (CGI-I) [ Time Frame: 4 to 6 weeks ]
    The CGI-Improvement (CGI-I) is similar to the CGI-S. Directly post-treatment and at the follow-up, the investigator compares the patient's overall clinical condition to the one week period just prior to the baseline visit. The query hypertension is rated on a seven-point scale: "Compared to the patient's condition at baseline, this participant's condition is: 1=very much improved since the baseline; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse since the baseline measure.

Secondary Outcome Measures :
  1. Psychophysiological Profile - Heart Rate Variability (HRV) [ Time Frame: 4 to 6 weeks ]
    HRV will be assessed using the emwave2 desktop device (HeartMath Institute, Boulder Creek, CA). It uses an earlobe plethysmograph sensor to detect the pulse wave, and plots changes in heart rate on a beat-to-beat basis.

  2. Psychophysiological Profile - Synchrony between Respiration and HRV [ Time Frame: 4 to 6 weeks ]
    A measure of synchrony will be assessed which will be calculated using the HRV measure previously described and respiration, which will be recorded by strain gauges placed around the abdomen.

  3. Psychophysiological Profile - Skin Conductance [ Time Frame: 4 to 6 weeks ]
    Galvanic skin response is measured in Siemens by the skin's conductance between two small metal electrodes placed on the walls of the index finger tip and the ring finger tip.

  4. Mini-Mental State Examination (MMSE) [ Time Frame: 4 to 6 weeks ]
    The Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for dementia.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Males and females between the ages of 50-90 with a molecular documentation of a fragile X premutation, diagnosed with FXTAS.
  2. stable current pharmacological treatment regimen for at least 4 weeks.
  3. English speaking (the intervention is currently only available in English)
  4. Clinically significant hypertension.
  5. Normal or corrected to normal vision and hearing.

Exclusion Criteria:

  1. Significant medical and behavioral problems that would interfere with the study (e.g. not being able to sit and play a computer game for 10 minutes)
  2. Participants who plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study
  3. Individual is non-verbal (has no spoken language)
  4. English is not the primary language.
  5. Clinically critical Hypertension that requires medical attention

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 identifier (NCT number): NCT03816540

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Contact: Andrea Schneider, PhD. 916-703-0202
Contact: Pryanka Narayan 916-703-0202

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United States, California
University of California, Davis, MIND Institute Recruiting
Sacramento, California, United States, 95817
Contact: Andrea Schneider, PhD.    916-703-0202   
Sponsors and Collaborators
University of California, Davis
UC Davis MIND Institute
UC Davis, Mini-Grant Geriatrics


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Responsible Party: University of California, Davis Identifier: NCT03816540     History of Changes
Other Study ID Numbers: 1151848
First Posted: January 25, 2019    Key Record Dates
Last Update Posted: January 25, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases