Deciphering Preserved Autonomic Function After Multiple Sclerosis (DPAF-MS)

This study looks to characterize gradients of dysfunction in the autonomic nervous system in patients with clinically diagnosed multiple sclerosis. The autonomic nervous system plays key roles in regulation of blood pressure, skin blood flow, and bladder health- all issues that individuals with multiple sclerosis typically suffer. Focusing on blood pressure regulation, the most precise metric with broad clinical applicability, the investigators will perform laboratory-based tests to probe the body's ability to generate autonomic responses. For both individuals with multiple sclerosis and uninjured controls, laboratory-based experiments will utilize multiple parallel recordings to identify how the autonomic nervous system is able to inhibit and activate signals. The investigators anticipate that those with autonomic dysfunction with multiple sclerosis will exhibit abnormalities in these precise metrics. The investigators will look to see if any substantial connections exist between different degrees of preserved autonomic function and secondary autonomic complications from multiple sclerosis. In accomplishing this, the investigators hope to give scientists important insights to how the autonomic nervous system works after multiple sclerosis and give physicians better tools to manage these secondary autonomic complications.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Autonomic Dysreflexia; Control Subjects
• Intervention / Treatment: Diagnostic test: Tests of sympathetic inhibition; Diagnostic test: Tests of sympathetic activation; Diagnostic test: Testing of autonomic dysreflexia

• Study Type: Interventional
• Enrollment (Estimated): 13
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Erin Lund; Phone Number: 507-284-9298; Email: lund.erin@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Recruiting
      • Mayo Clinic
      • Contact: Erin Lund; Phone Number: 507-284-9298; Email: lund.erin@mayo.edu
      • Principal Investigator: Ryan J. Solinsky, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-50 years old
• clinically confirmed diagnosis of multiple sclerosis -OR- uninjured control

Exclusion Criteria:

• symptoms of cardiovascular (including, but not limited to: hypertension, stroke, chest pain, etc.), respiratory, peripheral neurological or autonomic disease (particularly diabetes mellitus requiring treatment)
• women who are pregnant or lactating
• having a body mass index (BMI) ≥ 35 kg/m2
• taking or being administered a medication known to potentially have adverse interactions with phenylephrine
• in the judgement of the principal investigator or clinical collaborator, any illness or condition that will interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of the study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individuals with multiple sclerosis	Diagnostic test: Tests of sympathetic inhibition; Bolus phenylephrine infusion using the Oxford technique will generate the need to inhibit sympathetic activity. Similarly, resting state Mayer waves will be assessed with regard to heart rate and blood pressure responses.; Diagnostic test: Tests of sympathetic activation; Cold pressor test of the hand will be used to cause sympathetic activation. Valsalva's maneuver will assess the ability to buffer against blood pressure fall (phase II).; Diagnostic test: Testing of autonomic dysreflexia; Cold pressor test of the foot and bladder pressor response will be tested.
Experimental: Individuals without multiple sclerosis	Diagnostic test: Tests of sympathetic inhibition; Bolus phenylephrine infusion using the Oxford technique will generate the need to inhibit sympathetic activity. Similarly, resting state Mayer waves will be assessed with regard to heart rate and blood pressure responses.; Diagnostic test: Tests of sympathetic activation; Cold pressor test of the hand will be used to cause sympathetic activation. Valsalva's maneuver will assess the ability to buffer against blood pressure fall (phase II).; Diagnostic test: Testing of autonomic dysreflexia; Cold pressor test of the foot and bladder pressor response will be tested.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Valsalva Maneuver Phase II	Presence or absence of phase II on Valsalva maneuver testing, which takes approximately 15 seconds to complete. This will be repeated x3.	During single laboratory diagnostic testing session, on average 30 minutes after start of laboratory testing session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantify autonomic dysreflexia and orthostatic hypotension	Participants will be given the Autonomic Dysfunction Following Spinal Cord Injury questionnaire (score range 0-436, with higher scores indicating more autonomic dysfunction).	Baseline, prior to laboratory diagnostic testing session
Quantify secondary autonomic complications	Participants will be given the Composite Autonomic Symptom Score (range 0-100, with higher scores indicating more autonomic dysfunction).	Baseline, prior to laboratory diagnostic testing session
Beat-to-beat heart rate	Electrocardiogram will record continuous measures with changes in R-R interval (ms) quantified and compared to baseline.	Continuous recording during single laboratory diagnostic testing session, from baseline to lab session end, average of 3 hours in duration
Beat-to-beat blood pressure	Non-invasive continuous blood pressure monitors will be used, with changes in systolic and diastolic pressure (in mmHg) from resting baseline measured.	Continuous recording during single laboratory diagnostic testing session, from baseline to lab session end, average of 3 hours in duration
Serum Catecholamines	A series of 3 serum catecholamine draws will occur during the study visit at baseline, pre-pressor test, and post-pressor test to evaluate change in stress hormone.	3x during single laboratory diagnostic testing session - collected at Baseline, pre-pressor test, post-pressor test - pre-pressor & post-pressor timepoint labs collected on average 2.5 & 3 hours post-baseline, respectively
Serum Cortisol	A series of 3 serum cortisol draws will occur during the study visit at baseline, pre-pressor test, and post-pressor test to evaluate change in stress hormone.	3x during single laboratory diagnostic testing session - collected at Baseline, pre-pressor test, post-pressor test - pre-pressor & post-pressor timepoint labs collected on average 2.5 & 3 hours post-baseline, respectively
T-Cell Exhaustion Markers	Blood will be drawn at start of laboratory testing to assess T-cell exhaustion markers by incidence of surface markers including PD-1, TIM-3, LAG3, and CTLA-4 per individual.	During single laboratory diagnostic testing session - Baseline

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Ryan J. Solinsky, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 14, 2025
• First Submitted That Met QC Criteria: May 30, 2025
• First Posted (Actual): June 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Trauma, Nervous System; Autonomic Nervous System Diseases; Spinal Cord Injuries; Multiple Sclerosis; Autonomic Dysreflexia
• Other Study ID Numbers: 24-007459

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: No