CRI in POTS in Adolescents (POTS)

Evaluation of the Compensatory Reserve Index and Psychosocial Factors in Pediatric Autonomic Dysfunction

The investigators aim to study whether the Compensatory Reserve Index (CRI) (an FDA approved device that assesses intravascular volume) can be used to evaluate severity of Postural Orthostatic Tachycardia Syndrome (POTS) and whether the CRI value has a correlation with severity of psychosocial symptoms and functional impairment associated with POTS.

Study Overview

• Status: Completed
• Conditions: Postural Orthostatic Tachycardia Syndrome
• Intervention / Treatment: Device: CRI device (non-invasive vitals sign measurement)

Detailed Description

Autonomic dysfunction (or dysautonomia) describes several medical conditions linked to the autonomic nervous system. One of these is Postural Orthostatic Tachycardia Syndrome (POTS). In pediatric populations, symptoms of autonomic dysfunction include an increase in heart rate when standing up (tachycardia), dizziness, nausea, vomiting, fatigue, headaches, abdominal discomfort, and sleep disturbances. POTS is specifically characterized by orthostatic intolerance and a forty beats per minute (bpm) increase in heart rate upon standing. The etiology of POTS is poorly understood, and there is limited literature on the management of POTS in pediatric populations. In the U.S., POTS is estimated to affect 1-3 million people.

The ability of the CRI algorithm to accurately distinguish individuals with varying tolerances to reduced central blood volume can be attributed to a unique function of the algorithm, which analyzes and compares the entirety of each waveform in a window of time to trend subtle features that correspond with varying degrees of central volume loss. CRI can also detect vascular changes associated with postural orthostatic tachycardia syndrome. CRI will be evaluated in subjects at supine and standing positions along with traditional orthostatic measures.

Following CRI measurements, subjects and their parents will be asked to complete a series of surveys to assess their psychosocial symptoms and functional impairment. The CRI measurement and survey completion will occur over the course of one clinic visit.

• Study Type: Observational
• Enrollment (Actual): 77

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will include adolescents with POTS 12-21 years old and adolescents without POTS 12-21 years old. One parent will be required to attend the study visit.

Description

Inclusion Criteria:

• Adolescent participants must be aged 12 to 21 years (inclusive).
• Each participant must have at one parent/legal guardian who can provide informed consent for the adolescent and participate in the study by completing study questionnaires.
• Moreover, as the majority of study measures are only validated for use in English, only English-speaking patients will be included in this study.

Exclusion Criteria:

• Adolescents will be excluded from the study if they are outside the age range of 12-21 years old
• Adolescents who are wards of the state
• Adolescents who are incarcerated
• Adolescents who are decisionally impaired (i.e., have difficulty understanding the protocol during the consent process, and/or research team member is unsure of individual's ability to correctly identify whether the research study would need to stop or not)
• Adolescents who object at any time to participating in the study
• Adolescents who have a pacemaker
• Adolescents who are taking beta blocker medications
• Adolescents who were were hospitalized in the past month for serious medical conditions affecting their cardiopulmonary system (note, this does not include recent hospitalizations for trauma or burns).
• Adolescents will also be excluded if their parent/legal guardian(s) are unwilling to participate in the study and/or do not have legal custody of the adolescent participant.
• Adolescents who do not speak English will be excluded from the study as majority of the study measures are only validated in English.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adolescents with POTS; Adolescents with Postural Orthostatic Tachycardia Syndrome (POTS) who meet diagnostic criteria for an orthostatic heart rate increase of >30, between ages 12-21 are eligible for this group. They will have a urine specific gravity conducted at the beginning of the clinic visit to assess hydration status. If urine specific gravity shows adequate hydration, subjects will proceed with orthostatic measurements with concomitant CRI measurements (via a non-invasive pulse oximetry monitor). (Subjects who are dehydrated will be given electrolyte drinks for rehydration and urine specific gravity will be rechecked after survey completion and before CRI and orthostatic measurements.) Following the CRI and orthostatic measurements, subjects and their parents will be asked to complete a series of surveys via REDcap. Interventions performed: Urine specific gravity measurement; CRI measurements, orthostatic vitals measurements; Survey administration	Device: CRI device (non-invasive vitals sign measurement); Survey administration, Orthostatic vital measurements; Other Names: Survey administration, Orthostatic vital measurements
Adolescents without POTS, Control Group; Adolescents without Postural Orthostatic Tachycardia Syndrome (POTS) between ages 12-21 are eligible for this group. This group of subjects will have a urine specific gravity conducted at the beginning of the clinic visit to assess hydration status. If the urine specific gravity shows adequate hydration, subjects will proceed with orthostatic measurements with concomitant CRI measurements (via a non-invasive pulse oximetry monitor). (Subjects who are dehydrated will be given electrolyte drinks for rehydration and their urine specific gravity will be rechecked after survey completion and before CRI and orthostatic measurements.) Following the CRI and orthostatic measurements, subjects and their parents will be asked to complete a series of surveys via REDcap. Interventions performed: Urine specific gravity measurement; CRI measurements, orthostatic vitals measurements; Survey administration	Device: CRI device (non-invasive vitals sign measurement); Survey administration, Orthostatic vital measurements; Other Names: Survey administration, Orthostatic vital measurements
Adolescents diagnosed with POTS who do not meet HR; Adolescents diagnosed with Postural Orthostatic Tachycardia Syndrome (POTS) between ages 12-21, who do not meet diagnostic heart rate criteria, are eligible for this group. This group of subjects will have a urine specific gravity conducted at beginning of the clinic visit to assess hydration status. If the urine specific gravity shows adequate hydration, subjects will proceed with orthostatic measurements with concomitant CRI measurements (via a non-invasive pulse oximetry monitor). (Subjects who are dehydrated will be given electrolyte drinks for rehydration and urine specific gravity will be rechecked after survey completion and before CRI and orthostatic measurements.) Following the CRI and orthostatic measurements, subjects and their parents will be asked to complete a series of surveys via REDcap. Interventions performed: Urine specific gravity measurement; CRI measurements, orthostatic vitals measurements; Survey administration	Device: CRI device (non-invasive vitals sign measurement); Survey administration, Orthostatic vital measurements; Other Names: Survey administration, Orthostatic vital measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Compensatory Reserve Index (CRI) Values	This is a value between 0 and 1. The CRI values will be noted from minute 1 to minute 20. This study has only one visit.	Minute 1 through minute 20
Physical Symptoms Score as assessed by a Survey	Subjects will complete a survey to assess severity of physical symptoms (fatigue, dizziness, weakness, headache, chest pain, palpitations, sweating, shortness of breath, abdominal pain, nausea, vomiting, period pain, cries easily, altered temperature, discoloration of extremities, peripheral edema, numbness, brain fog, diarrhea, constipation, blurred vision, muscle pain, joint pain, exercise intolerance, insomnia, joint hypermobility, sensitivity to light, early society, etc.). Possible scores range from 0 to 10, with 10 indicating the most severe/debilitating symptoms and 0 indicating no physical symptoms/normal functionality. The survey will be completed during the study visit. This study has only one visit.	1 day (study visit)
Frequency of Anxiety in Days as assessed by a Survey	Subjects will complete a survey to assess how frequently (how many days) they experienced feelings of acute anxiety over the past month. The survey will be completed during the study visit. This study has only one visit.	1 day (study visit)
Hypermobility as evaluated by the Beighton scale	The Beighton Score is a validated measure used to evaluate hypermobility in children on a scale of 0-9 for different joints using 3 score bands. A higher Beighton score is associated with hypermobility. The assessment will be completed during the study visit. This study has only one visit.	1 day (study visit)
Frequency of Feelings of Stress in Days as assessed by a survey	Subjects will complete a survey to assess how frequently (how many days) they experienced feelings of stress over the past month. The survey will be completed during the study visit. This study has only one visit.	1 day (study visit)
Frequency of difficulty with sleep as assessed by a survey	Subjects will complete a survey to assess how long it takes them to fall asleep, how often they wake up, how long it takes to fall back asleep after waking up, and the frequency of difficulties with sleep.The survey will be completed during the study visit. This study has only one visit.	1 day (study visit)
Revised Child Anxiety and Depression Scale (RCADS and RCADS-P)	Subjects and their parent(s) will complete this well-established survey tool to assess the frequency of symptoms of anxiety and depression. The survey will be completed during the study visit. This study has only one visit.	1 day (study visit)
Functional disability inventory (FDI)	Participants and their parent(s) will be asked to complete a 15-question survey to evaluate the difficulty of daily tasks with a scale of impossible (4), a lot of trouble (3), some trouble (2), a little trouble (1), and no trouble (0) (39). This measure will be adapted very slightly to reflect the ubiquity of electronic media for today's adolescents, i.e., question 11 will be modified from "Watching TV" to "Watching TV and other screens." This measure yields an overall summed score. The survey will be completed during the study visit. This study has only one visit.	1 day (study visit)
Social Connectedness Scale	The Social Connectedness Scale, developed by Lee, assesses the responder's perceptions of social connectedness (i.e., the perception of interpersonal closeness with the social world) through 15 self-report items. The assessment will be completed during the study visit. This study has only one visit.	1 day (study visit)
Friendship scale	The "Close Friend Support/Regard" subscale of the Social Support Scale for Children and Adolescents will be used to assess the adolescent's perception that he/she has a close friend who he/she can tell problems to, who truly understands him/her, who he/she can complain to about things that bother them, who he/she can spend time with, and who really listens to what he/she says. This subscale comprises 6 items rated on a Likert scale from "really true for me" and "sort of true for me" for the positive phrasing of the item (e.g., "Some teenagers have a close friend who really understands them") to "sort of true for me" and "really true for me" for the negative phrasing of the item (e.g., "Other teenagers don't have a close friend who really understands them."). Given that some participants will be above 18 years, we will modify the wording to "some people". The assessment will be completed during the study visit. This study has only one visit.	1 day (study visit)
Frequency of friendship contact	Participants will be asked to indicate, over the past month, on how many occasions they have spent time with a close friend outside of school (i.e., free entry). The survey will be completed during the study visit. This study has only one visit.	1 day (study visit)
Family Assessment Device General Functioning scale (GFS)	The Family Assessment GFS is a twelve-point scale that evaluates the "overall health or pathology in family functioning" via analysis of six dimensions of family functioning: problem solving, communication, roles, affective responsiveness, affective involvement, and behavior control. This will be completed by subjects and their parent(s). The survey will be completed during the study visit. This study has only one visit.	1 day (study visit)
Sexual maturity Rating (Tanner stage)	This questionnaire with image demonstrations of the different Tanner stages will ask patients to self-report their appropriate Tanner stages.The questionnaire will be completed during the study visit. This study has only one visit.	1 day (study visit)
Parent Behavior Adult Responses to Children's Symptoms (ARCS)	The ARCS is a 29-point scale with a goal of assessment of parent responses to their children's symptoms (i.e. protectiveness, minimization, encouragement, and monitoring).The assessment will be completed during the study visit. This study has only one visit.	1 day (study visit)
Parent Mental Health- PHQ-9	The Parent Mental Health scales, Parent Health Questionnaire 9 item scale (PHQ-9) and Generalized Anxiety Disorder 7 item scale (GAD-7), are short self-reported questionnaires that are widely used with established psychometrics in the parent population. The PHQ-9 assessment will be completed during the study visit. This study has only one visit.	1 day (study visit)
Parent Mental Health- GAD-7	The Parent Mental Health scales, Parent Health Questionnaire 9 item scale (PHQ-9) and Generalized Anxiety Disorder 7 item scale (GAD-7), are short self-reported questionnaires that are widely used with established psychometrics in the parent population. The GAD-7 assessment will be completed during the study visit. This study has only one visit.	1 day (study visit)

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Colorado Clinical & Translational Sciences Institute
• Investigators: Principal Investigator: Clio Pitula, PhD, Children's Hospital Colorado

Publications and helpful links

General Publications

• Convertino VA, Moulton SL, Grudic GZ, Rickards CA, Hinojosa-Laborde C, Gerhardt RT, Blackbourne LH, Ryan KL. Use of advanced machine-learning techniques for noninvasive monitoring of hemorrhage. J Trauma. 2011 Jul;71(1 Suppl):S25-32. doi: 10.1097/TA.0b013e3182211601.
• Moulton SL, Mulligan J, Grudic GZ, Convertino VA. Running on empty? The compensatory reserve index. J Trauma Acute Care Surg. 2013 Dec;75(6):1053-9. doi: 10.1097/TA.0b013e3182aa811a.
• Grigoriou E, Boris JR, Dormans JP. Postural orthostatic tachycardia syndrome (POTS): association with Ehlers-Danlos syndrome and orthopaedic considerations. Clin Orthop Relat Res. 2015 Feb;473(2):722-8. doi: 10.1007/s11999-014-3898-x. Epub 2014 Aug 26.
• Johnson JN, Mack KJ, Kuntz NL, Brands CK, Porter CJ, Fischer PR. Postural orthostatic tachycardia syndrome: a clinical review. Pediatr Neurol. 2010 Feb;42(2):77-85. doi: 10.1016/j.pediatrneurol.2009.07.002.
• Kizilbash SJ, Ahrens SP, Bruce BK, Chelimsky G, Driscoll SW, Harbeck-Weber C, Lloyd RM, Mack KJ, Nelson DE, Ninis N, Pianosi PT, Stewart JM, Weiss KE, Fischer PR. Adolescent fatigue, POTS, and recovery: a guide for clinicians. Curr Probl Pediatr Adolesc Health Care. 2014 May-Jun;44(5):108-33. doi: 10.1016/j.cppeds.2013.12.014.
• Boris JR, Bernadzikowski T. Demographics of a large paediatric Postural Orthostatic Tachycardia Syndrome Program. Cardiol Young. 2018 May;28(5):668-674. doi: 10.1017/S1047951117002888. Epub 2018 Jan 23.
• Kritzberger CJ, Antiel RM, Wallace DP, Zacharias JD, Brands CK, Fischer PR, Harbeck-Weber C. Functional disability in adolescents with orthostatic intolerance and chronic pain. J Child Neurol. 2011 May;26(5):593-8. doi: 10.1177/0883073810390366. Epub 2011 Feb 7.
• Pederson CL, Brook JB. Health-related quality of life and suicide risk in postural tachycardia syndrome. Clin Auton Res. 2017 Apr;27(2):75-81. doi: 10.1007/s10286-017-0399-5. Epub 2017 Feb 6.
• Bruce BK, Weiss KE, Harrison TE, Allman DA, Petersen MA, Luedkte CA, Fischer PR. Interdisciplinary Treatment of Maladaptive Behaviors Associated with Postural Orthostatic Tachycardia Syndrome (POTS): A Case Report. J Clin Psychol Med Settings. 2016 Jun;23(2):147-59. doi: 10.1007/s10880-015-9438-3.
• Lewis I, Pairman J, Spickett G, Newton JL. Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. J Intern Med. 2013 May;273(5):501-10. doi: 10.1111/joim.12022. Epub 2013 Jan 7.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 22, 2020

Study Registration Dates

• First Submitted: May 24, 2019
• First Submitted That Met QC Criteria: June 4, 2019
• First Posted (Actual): June 5, 2019

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 22, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: POTS; Postural Orthostatic Tachycardia Syndrome; Dysautonomia; Compensatory Reserve Index; CRI
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Tachycardia; Postural Orthostatic Tachycardia Syndrome
• Other Study ID Numbers: 18-2618

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes