HIV Associated Polyneuropathy
Conditions
Keywords
HIV-Associated Peripheral Neuropathy, Neuropathic pain, Auricular Vagus Nerve Stimulation, Vagus Nerve Stimulation, Neuromodulation, Aging, Heart Rate Variability, Quantitative Sensory Testing, Neuroinflammation, Corticospinal Excitability
Brief summary
This study looks at a non-invasive ear stimulation treatment to better understand nerve pain in people living with HIV. The study aims to assess how the body and nervous system respond to this treatment, including changes in heart function and pain signals. The goal is to learn how future treatments for nerve pain may be improved.
Interventions
DEVICETranscutaneous Auricular Vagus Nerve Stimulation (AVNS)
Transcutaneous auricular vagus nerve stimulation (taVNS) will be administered at the cymba concha using hydrogel electrodes and a Digitimer DS8R biphasic constant-current stimulator. Participants will receive 90-minute stimulation sessions consisting of monophasic pulses (pulse width: 500 microseconds; frequency: 25 Hz; duty cycle: 50%). Stimulation intensity will be set at 200% of the participant's sensory perception threshold and may be adjusted up to 5 milliamperes (mA) while remaining below the pain threshold.
Sponsors
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Established HIV infection * Glove/stocking dysesthesias lasting for ≥3 months * HIV-associated peripheral neuropathy (HIV-PN) related symptoms ≥4 (on a scale of 0-10) within the last week * Stable medical care (i.e., no changes in Antiretroviral Therapy or pain medication within 2 months of enrollment) * Able to read the consent form, demonstrate understanding of study procedures and requirements, and independently provide written informed consent
Exclusion criteria
* Unstable cardiac disease * Implanted electronic or magnetic devices (e.g., pacemaker, cochlear implants, medication pumps, and other implanted neurostimulation systems) * Head or neck cancer or metastases * Recent ear trauma or metal implants in the head * History of epilepsy, unprovoked seizure, stroke, brain tumor, significant traumatic brain injury, prior intracranial surgery, or other neurological condition associated with increased seizure risk * Active or uncontrolled comorbidities that independently cause neuropathy (e.g., recent chemotherapy, uncontrolled diabetes with documented neuropathic complications) * Clinical evidence of non-HIV neuropathy (e.g., neuropathic symptoms predating HIV diagnosis, uncontrolled diabetes) * Known allergy to tape/adhesive * Ferromagnetic or non-MRI-compatible metal in the head, neck, eye, or cranial region, including aneurysm clips, retained metal fragments, bullets, shrapnel, or other metallic implants not demonstrated to be TMS-compatible. * Pregnancy or actively breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Short Interval intraCortical Inhibition (SICI) | Baseline (Day 0), Post-trial (Day 14) | Short-interval intracortical inhibition (SICI) will be assessed using paired-pulse transcranial magnetic stimulation (TMS) with a MagPro X100 stimulator. Change in SICI will be calculated as the difference between post-intervention and pre-intervention measurements. Negative values indicate increased intracortical inhibition. |
| Change in Root Mean Square of Successive Differences (RMSSD) | (Days 1-13), Post-trial (Day 14) | The root mean square of successive differences (RMSSD), will be assessed using a three-lead electrocardiogram (ECG). Change in RMSSD will be calculated as the difference between post-intervention and baseline measurements. Higher RMSSD values indicate greater parasympathetic (vagal) activity and heart rate variability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Neuropathic Pain Symptom Severity (NPSI) | Baseline (Day 0), post-trial (Day 14) | Neuropathic pain symptom severity will be assessed using the Neuropathic Pain Symptom Inventory (NPSI), a patient-reported questionnaire that evaluates 10 neuropathic pain symptoms on an 11-point numeric scale ranging from 0 (no symptom) to 10 (worst symptom severity imaginable). The NPSI also includes 2 items assessing the duration of ongoing pain and the frequency of pain attacks. Higher scores indicate greater neuropathic pain symptom severity. |
| Change in Neuropathic Symptom Intensity (Numeric Rating Scale) | Baseline (Day 0), pre/post each treatment session (Days 1-13), post-trial (Day 14), and at follow up (Day 45) | Neuropathic symptom intensity will be assessed using the 0-10 Numeric Rating Scale (NRS). Participants will rate the average severity of HIV-associated peripheral neuropathy symptoms from 0 (not bothersome) to 10 (worst imaginable). Higher scores indicate greater symptom intensity. |
| Change in Serum Neurofilament Light Chain (NfL) | Baseline (Day 0), Post-trial (Day 14) | Serum neurofilament light chain (NfL) will be measured from non-fasted venous blood samples. NfL concentrations (pg/mL) will be quantified using enzyme-linked immunosorbent assay (ELISA). Change in NfL will be calculated as the difference between post-intervention and baseline serum concentrations. Higher concentrations indicate greater neuroaxonal injury. |
| Change in Serum Interleukin-1 Beta (IL-1β) | Baseline (Day 0), Post-trial (Day 14) | Serum interleukin-1 beta (IL-1β) will be measured from non-fasted venous blood samples. IL-1β concentrations (pg/mL) will be quantified using enzyme-linked immunosorbent assay (ELISA). Change in IL-1β will be calculated as the difference between post-intervention and baseline serum concentrations. Higher concentrations indicate greater systemic inflammation. |
| Change in Serum Tumor Necrosis Factor-Alpha (TNF-α) | Baseline (Day 0), Post-trial (Day 14) | Serum Tumor Necrosis Factor-Alpha (TNF-α) will be measured from non-fasted venous blood samples. TNF-α concentrations (pg/mL) will be quantified using enzyme-linked immunosorbent assay (ELISA). Change in TNF-α will be calculated as the difference between post-intervention and baseline serum concentrations. Higher concentrations indicate greater systemic inflammation. |
| Change in Wind-Up Ratio (WUR) | Baseline (Day 0), Pre/post each treatment session (Days 1-13), Post-trial (Day 14) | Wind-up ratio (WUR), will be assessed using responses to repeated pinprick stimuli. Change in WUR will be calculated as the difference between post-intervention and baseline measurements. Lower WUR values indicate reduced temporal summation and decreased central sensitization. |
| Change in Conditioned Pain Modulation (CPM) | Baseline (Day 0), Post-trial (Day 14) | Conditioned pain modulation (CPM), will be assessed using a cold pressor conditioning stimulus (1 to 4°C for 60 seconds) and pressure pain threshold (PPT) testing on the forearm. The CPM effect will be calculated as the percent change in PPT from before to after the conditioning stimulus (%ΔPPT). Higher CPM values indicate greater endogenous pain inhibition. |
Countries
United States
Contacts
CONTACTMarlon L Wong, PT, PhD
CONTACTRichard Martinez, MS
PRINCIPAL_INVESTIGATORMarlon L. Wong, PT, PhD
University of Miami
Outcome results
None listed