Symptom Management Efficacy Study to Reduce Distal Neuropathic Pain

Study Overview
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Brief Summary
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Distal sensory peripheral neuropathy (DSP) is a chronic, debilitating painful condition affecting quality of life in persons living with HIV. Treatments prescribed to manage DSP pain, such as nonnarcotic and narcotic analgesics, antidepressants and anticonvulsants, are largely ineffective. In HIV there are no FDA-approved drugs for this indication. This study assesses in a randomized controlled clinical trial, the efficacy of novel non-pharmacologic pain management approaches to reduce HIV-related DSP pain and improve quality of life.

Detailed Description
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Distal sensory peripheral neuropathy (DSP) is a chronic, debilitating painful condition affecting quality of life in 20%-50% of persons living with HIV. Treatments prescribed to manage DSP pain, such as nonnarcotic and narcotic analgesics, antidepressants and anticonvulsants, are largely ineffective. Effective management of DSP pain is an unmet therapeutic need for this population. This study is a randomized, blinded, placebo-controlled clinical trial of the efficacy of Acupuncture/Moxibustion (Acu/Moxa) for HIV DSP pain/discomfort. Subjects with HIV-related lower limb DSP pain are randomized to one of four Conditions: 1) Standard (fixed) protocol Acu/Moxa, 2) Individualized (tailored) protocol Acu/Moxa, 3) Sham Acu/Placebo Moxa (control), or 4) WaitList (control). Subjects attend six weeks of twice weekly treatment sessions and 3 non-treatment follow-up sessions at weeks 9, 11, and 15. All subjects are assessed by a blinded diagnostic acupuncturist (DA) and those assigned to Conditions 1, 2 and 3 receive treatments by an unblinded treating acupuncturist (TA). Specific Aims are: #1 determine group differences in weekly average pain (Gracely Pain Scale) at the end of treatment (Tx) and end of follow-up (F/U); SA#2 determine group differences in improvement in specific sensory symptoms (Subjective Peripheral Neuropathy Screen and neurological sensory testing (NST)) and patient-rated effectiveness (Clinical Global Improvement, NIH PROMIS Pain Intensity and Health-Related Quality of Life (MOS-HIV)) at Tx and F/U; SA#3 determine group differences in safety profiles; and SA#4, explore how baseline measures, TCM diagnoses, NST and pain medication use predict response to treatment.

Official Title
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Symptom Management Efficacy Study to Reduce Distal Neuropathic Pain

Conditions
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HIV/AIDS, Neuropathic Pain, HIV Neuropathy, Pain

Intervention / Treatment
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* Other: Standard Acupuncture / Moxibustion
* Other: Individualized (Tailored) Active Acupuncture / Moxibustion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, 18 years of age or older, HIV+ or AIDS diagnosed, with a history of DSP of the lower extremities for the past three months or greater. Primary care provider (PCP) verification of HIV status, diagnosis of DSP, & subject clinical suitability for the study. Evidence of lower limb neuropathy (bilateral ankle reflexes absent or depressed relative to the knee, decreased sensation to vibration, pin prick and temperature with distal sensory loss grading to normal in the proximal limb) GPS rated pain severity of moderate or above, documented in 1-week prospective self-report symptom diary (SD). Any antiretroviral Rx must have 3 months of stable regimen (same drugs, dose & frequency) prior to enrollment. Any pain medications must have 3 months of stable regimen prior to enrollment. Those on a stable pharmacologic regimen are expected to remain on the regimen for the duration of the study. Must understand and agree to complete daily symptom diaries for the duration of the study. Successfully complete a mini-mental status exam (obtaining a score of 24 or above). Exclusion Criteria: Any acute condition requiring medical care (eg. opportunistic infection). Conditions that may mimic HIV DSP symptoms: i.e. diabetes(3), coagulopathies, B12 deficiency, etc. Use any topically applied medications to the lower extremities. Alcohol and/or substance dependence. Use of injectable corticosteroids or any medications known to be neurotoxic within 3 months prior to enrollment. Pregnant women or unwilling to use an acceptable form of birth control. Receiving acupuncture within 6 months prior to enrollment. Any history of receiving moxibustion. Currently receiving any other complementary therapies such as herbs, massage, reiki etc. Relocation or plans that interfere with attending all of the planned study sessions and/or recording SD information.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, blinded, placebo-controlled clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard (fixed) protocol Acu/Moxa - Active<br>Standard (Fixed) Acupuncture / Moxibustion Active Protocol Subjects receive active standard Acu/Moxa protocol aimed at reducing neuropathic pain/discomfort. | Other: Standard Acupuncture / Moxibustion<br>* Standard (Fixed) Active Acupuncture / Moxibustion protocol aimed at reducing lower limb neuropathic pain/discomfort.<br>* Other names: Standard Acupuncture /Moxibustion;|
| Experimental: Individualized (tailored) protocol Acu/Moxa - Active<br>Individualized (Tailored) Active Acupuncture / Moxibustion Protocol Subjects receive active individualized Acu/Moxa protocol based on traditional Chinese medicine assessment aimed reducing neuropathic pain/discomfort. | Other: Individualized (Tailored) Active Acupuncture / Moxibustion<br>* Individualized (tailored) protocol Acu/Moxa - Active. Acu/Moxa prescription based on TCM assessment. Protocol aimed at reducing lower limb neuropathic pain/discomfort.<br>* Other names: Individualized Active Acupuncture / Moxibustion;|
| No Intervention: Sham Acu/Placebo Moxa (Control)<br>Sham Acu/Placebo Moxa (Control) Note. All subjects randomized to the Control will be offered 12 active protocol acupuncture/ moxibustion treatments, at no cost, at the end of their study participation. | |
| No Intervention: WaitList (Control)<br>WaitList (Control) No treatment. Subjects receive all aspects of study participation with the exception of exposure to Acupuncture / Moxibustion. Note. All subjects randomized to the Control will then be offered 12 active protocol acupuncture/ moxibustion treatments, at no cost, at the end of their study participation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gracely Pain Scale (GPS) | The GPS is a Likert magnitude-estimation log-scale of sensory pain. Subjects rate their DSP pain by selecting one of 13 words to describe their average and worst DSP pain. Nothing=0 to Extremely intense=12 | Change from baseline rating of pain/discomfort (Gracely Pain Scale) after 6 wks of twice-wkly treatment sessions (the end of the treatment phase) and at weeks 9, 11 and 15 (the follow-up phase - determine sustainability). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Peripheral Neuropathy Screen (SPNS) | Describes neuropathy symptoms eg. aching/burning, pins and needles, numbness, location (hands/arms, feet/legs), and severity of symptoms from minimal to extreme. | Change from baseline rating of neuropathy symptoms after 6 wks of twice-wkly treatment sessions (the end of the treatment phase) and at weeks 9, 11 and 15 (the follow-up phase - determine change and sustainability) | 
| NIH PROMIS Pain Scale | NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity short form is used to assess how much a person hurts. Subjects in the last 7 days, the worst pain intensity, the average pain intensity. Subjects rate their pain intensity from none (=1) to very severe (=5). | Change from baseline rating of pain intensity after 6 wks of twice-wkly treatment sessions (the end of the treatment phase) and at weeks 9, 11 and 15 (the follow-up phase - determine change and sustainability) | 
| Medical Outcome Survey - HIV (MOS-HIV) | General health-related quality of life questions in HIV that assesses ten dimensions of health (overall health, pain, physical functioning, role and social functioning, mental health, energy/fatigue, cognitive function, health distress | Change from baseline rating of general health after 6 wks of twice-wkly treatment sessions (the end of the treatment phase) and at weeks 9, 11 and 15 (the follow-up phase - determine change and sustainability) | 
| Clinical Global Severity Improvement Scale (CGIs) | The severity of illness scale measures global severity of symptoms [in the context of peripheral neuropathy]. The patient rates discomfort from peripheral neuropathy on a scale of 0= No discomfort to 6= Very severe discomfort. The global improvement component measures the level of change from initial severity: 0= No improvement at all to 6= Great improvement | Change from baseline rating of pain intensity after 6 wks of twice-wkly treatment sessions (the end of the treatment phase) and at weeks 9, 11 and 15 (the follow-up phase - determine change and sustainability) | 
| Neurological Sensory Testing (NST) | Neurological assessments with Neuro Sensory Testing (NST) include: muscle strength and reflexes and sensory testing for lower limb vibration, pain and thermal sensation. Standard neurological assessment: muscle strength 0-5; reflexes 0-5; pain- intact, reduced, absent, hyperalgesia; vibration - intact, impaired; thermal - intact, reduced absent. The neuro/NST also serves to monitor for clinical safety and findings. | Change from baseline neurological physical assessment after 6 wks of twice-wkly treatment sessions (the end of the treatment phase) and at weeks 9, 11 and 15 (the follow-up phase - determine change and sustainability) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuropathic pain, HIV Neuropathy, HIV/AIDS, Symptom Management, Acupuncture, Pain, Pain Syndrome