Effect of Cannabis and Endocannabinoids on HIV Neuropathic Pain

ID: NCT03099005
Status: Not yet recruiting
Phase: Phase 2
Start Date: March 01, 2018
First Submitted: March 28, 2017
Last Updated: December 26, 2017
Results: N/A
Sponsors & Collaborators: Barth Wilsey MD
Location: United States
Conditions: Cannabis, HIV Neuropathy, Pain Syndrome
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Study Description

Brief Summary

Acute cannabis administration is reported to alleviate HIV neuropathic pain (HIV-NP), but there is limited knowledge about the effects of cannabis constituents (delta-9 tetrahydrocannabinol/THC and cannabidiol/CBD), the consequences of long-term cannabis use, and the impact of cannabis on endocannabinoid (EC) function in people living with HIV- NP. Our objective is to address these three fundamental gaps in our knowledge by: 1) examining the acute effects of various CBD/THC products on HIV-NP, 2) utilizing a mHealth text messaging protocol, Individual Monitoring of Pain and Cannabis Taken (IMPACT) to monitor daily real-world cannabis use and changes in pain; and 3) studying the relationship between cannabinoids, EC biomarkers, and chronic neuropathic pain

Detailed Description

Our objective is to assess 120 community-dwelling people living with HIV who have neuropathic pain and are currently using cannabis. These participants will be enrolled in a study that consists of two phases:

Phase 1) This will involve a cross over study involving three different doses of vaporized cannabis that contain THC and varying concentrations of CBD, including a) 3.74% THC + 0.49% CBD, b) 3.49% THC + 4.17% CBD, and c) 3.11% THC + 15.76% CBD. This phase will examine the acute effects of cannabis on pain intensity, blood endocannabinoid levels, and the relationship of pain with heart rate variability (HRV).

Phase 2) This phase will involve the association between dispensary-obtained cannabis and changes in pain reported via IMPACT, a mHealth text messaging program that will serve as a useful tool to monitor the relationship between pain and cannabis use. Text messaging is an effective method to modify health behaviors, monitor substance use, and track pain. Our group has recently demonstrated the feasibility of using short message service (SMS) texting to promote anti-retroviral therapy adherence and monitor daily methamphetamine (METH) use in persons living with HIV neuropathy with bipolar disorder or METH dependence.
Condition or disease Intervention/treatment Phase

Cannabis

HIV Neuropathy

Pain Syndrome

Drug: Cannabis
Other Names
marijuana
Phase 2

Tracking Information

First Submitted DateMarch 28, 2017
Last Update Posted DateDecember 26, 2017
Anticipated Start DateMarch 01, 2018
Anticipated Completion DateDecember 31, 2020
Anticipated Primary Completion DateSeptember 30, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Phase 1 - numerical 11-point Pain Intensity Scale [Time Frame: participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day]

    an ordinal scale

  • Phase 2 - numerical 11-point Pain Intensity Scale [Time Frame: participants will be queried on a daily basis for six months using text messaging]

    participants receive interactive text questions sent once a day to their cell phone asking them to indicate their average pain level for the day on a 0 to 10 scale

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Phase 1 - Patient Global Impression of Change (PGIC) [Time Frame: participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and this outcome will be measured 3 times after study medication is provided during the treatment day]

    a 7 point ordinal scale reflective of improvement in pain

  • Phase 1 - von Frey test [Time Frame: participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day]

    The von Frey filament will be applied on the dorsum of the more painful foot until bending is observed for 3 seconds, followed by a VAS pain rating

  • Phase 1 - Marijuana subscale (M-scale) of the Addiction Research Center Inventory (ARCI) [Time Frame: participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day]

    The M -scale has 12 true/false statements describing the subjective effects of marijuana

  • Phase 1 - Neuropsychological Assessment Battery [Time Frame: participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day]

    Testing will include the Wechsler Adult Intelligence Scale (WAIS-III) Digit Symbol, Hopkins Verbal Learning Test-Revised and Grooved Pegboard Test (motor)

  • Phase 1 - heart rate variability [Time Frame: participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day]

    Heart Rate Variability (HRV) correlates with the level of pain intensity. Persons with effective analgesic treatment of chronic pain exhibited improved HRV relative to pain sufferers with ineffective treatment suggesting HRV may serve as a pain biomarker

  • Phase 1 - store plasma samples for evaluation of THC, CBD, and endocannabinoid system biomarkers [Time Frame: participants will be followed for the duration of an 4 hour, single day human laboratory experiment, and the outcome will be measured once before they receive study medication and then 3 additional times during the treatment day]

    Cannabinoid and endocannabinoid levels in plasma will be quantified using a liquid chromatography-tandem mass spectrometry (LC/MS)

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEffect of Cannabis and Endocannabinoids on HIV Neuropathic Pain
Official TitleEffect of Cannabis Administration and Endocannabinoids on HIV Neuropathic Pain Primary Study - Phase 2
Brief Summary

Acute cannabis administration is reported to alleviate HIV neuropathic pain (HIV-NP), but there is limited knowledge about the effects of cannabis constituents (delta-9 tetrahydrocannabinol/THC and cannabidiol/CBD), the consequences of long-term cannabis use, and the impact of cannabis on endocannabinoid (EC) function in people living with HIV- NP. Our objective is to address these three fundamental gaps in our knowledge by: 1) examining the acute effects of various CBD/THC products on HIV-NP, 2) utilizing a mHealth text messaging protocol, Individual Monitoring of Pain and Cannabis Taken (IMPACT) to monitor daily real-world cannabis use and changes in pain; and 3) studying the relationship between cannabinoids, EC biomarkers, and chronic neuropathic pain

Detailed Description

Our objective is to assess 120 community-dwelling people living with HIV who have neuropathic pain and are currently using cannabis. These participants will be enrolled in a study that consists of two phases:

Phase 1) This will involve a cross over study involving three different doses of vaporized cannabis that contain THC and varying concentrations of CBD, including a) 3.74% THC + 0.49% CBD, b) 3.49% THC + 4.17% CBD, and c) 3.11% THC + 15.76% CBD. This phase will examine the acute effects of cannabis on pain intensity, blood endocannabinoid levels, and the relationship of pain with heart rate variability (HRV).

Phase 2) This phase will involve the association between dispensary-obtained cannabis and changes in pain reported via IMPACT, a mHealth text messaging program that will serve as a useful tool to monitor the relationship between pain and cannabis use. Text messaging is an effective method to modify health behaviors, monitor substance use, and track pain. Our group has recently demonstrated the feasibility of using short message service (SMS) texting to promote anti-retroviral therapy adherence and monitor daily methamphetamine (METH) use in persons living with HIV neuropathy with bipolar disorder or METH dependence.

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
120
Allocation
Randomized
Interventional Model
Crossover Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Cannabis
HIV Neuropathy
Pain Syndrome
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Cannabis

vaporization of cannabis

Other Names
marijuana
Study Groups/Cohorts
Low CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.6% THC + 0.09 CBD. They will then undergo experimental testing as described below under Outcome Measures.

Medium CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis 4 puffs will contain 1.6% THC + 0.09 CBD and 4 puffs will contain 1.73% THC + 5.4% CBD. They will then undergo experimental testing as described below under Outcome Measures.

High CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.73% THC + 5.4% CBD. They will then undergo experimental testing as described below under Outcome Measures.

Study Arms
Active Comparator High CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.73% THC + 5.4% CBD. They will then undergo experimental testing as described below under Outcome Measures.
Drug : Cannabis
vaporization of cannabis

Active Comparator Low CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.6% THC + 0.09 CBD. They will then undergo experimental testing as described below under Outcome Measures.
Drug : Cannabis
vaporization of cannabis

Active Comparator Medium CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis 4 puffs will contain 1.6% THC + 0.09 CBD and 4 puffs will contain 1.73% THC + 5.4% CBD. They will then undergo experimental testing as described below under Outcome Measures.
Drug : Cannabis
vaporization of cannabis

Arm Intervention/Treatment
Active Comparator High CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.73% THC + 5.4% CBD. They will then undergo experimental testing as described below under Outcome Measures.
Drug : Cannabis
Active Comparator Low CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis containing 1.6% THC + 0.09 CBD. They will then undergo experimental testing as described below under Outcome Measures.
Drug : Cannabis
Active Comparator Medium CBD session
In the morning, participants will inhale 8 puffs of vaporized cannabis 4 puffs will contain 1.6% THC + 0.09 CBD and 4 puffs will contain 1.73% THC + 5.4% CBD. They will then undergo experimental testing as described below under Outcome Measures.
Drug : Cannabis

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment120
Completion DateDecember 31, 2020
Eligibility Criteria: Inclusion Criteria:
1. the ability to provide informed consent
2. age 18 or older
3. HIV infection documented at the HNRP or assessed by an HIV test at screening;
4. a diagnosis of HIV sensory neuropathy
5. current use of cannabis
6. the ability to describe the THC and CBD content in the products they use, i.e., obtaining cannabis from dispensaries that list THC and CBD content
7. ability to respond to daily text message

Exclusion Criteria:
1. meeting criteria for current substance or alcohol dependence
2. traumatic brain injury
3. dementia or Alzheimer's disease
4. psychosis
5. a respiratory condition, i.e., pulmonary disease, that would be exacerbated by inhaling vaporized cannabis
6. history of cardiovascular disease, including myocardial infarction or stroke;
7. uncontrolled hypertension, defined as a systolic blood pressure greater than 160 mm Hg or a diastolic blood pressure greater than 100 mm Hg
8. pregnancy, breastfeeding, or unwillingness to prevent pregnancy during the cannabis administration portion of the study (using birth control in female participants of child- bearing age)
9. unwillingness or inability to receive or respond to text messages
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT03099005
Other Study ID Numbers
170510
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyBarth Wilsey MD, University of California, San Diego
Study Sponsor
Barth Wilsey MD
Collaborators
Not Available
Investigators
Principal Investigator
Brook L Henry, PhD
University of California, San Diego