Effect of Cannabis and Endocannabinoids on HIV Neuropathic Pain

• ClinicalTrials.gov Identifier: NCT03099005
• Recruitment Status: Recruiting
• First Posted: April 4, 2017
• Last Update Posted: October 18, 2018
• Sponsor: University of California, San Diego
• Information provided by (Responsible Party): Brook Henry, University of California, San Diego

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

Condition or disease	Intervention/treatment	Phase
Cannabis; HIV Neuropathy; Pain Syndrome	Drug: Cannabis	Phase 2

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:

• Low CBD session: 8 puffs of 1.6% THC + 0.09 CBD
• Medium CBD sessions: 4 puffs of 1.6% THC + 0.09 CBD plus 4 puffs of 1.73% THC + 5.4% CBD
• High CBD sessions: 8 puffs of 1.73% THC + 5.4% 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Acutely administered CBD/THC will reduce HIV-neuropathic pain in a stair-step manner; the highest CBD dose will provide the greatest pain reduction (high CBD > medium CBD > low CBD).
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Participants will receive vaporized cannabis using Volcano vaporizers (Storz and Bickel) with either 3.74% THC + 0.49% CBD, 3.49% THC + 4.17% CBD, or 3.11% THC + 15.76% CBD at each of three visits. Allocation assignment of visits will be assigned using a Web-based random number- generating program, "Research Randomizer" (http:// www.randomizer.org/). The allocation schedule will be kept in the pharmacy and concealed from other study personnel.
• Primary Purpose: Treatment
• Official Title: Effect of Cannabis Administration and Endocannabinoids on HIV Neuropathic Pain Primary Study - Phase 2
• Actual Study Start Date: July 1, 2018
• Estimated Primary Completion Date: September 30, 2020
• Estimated Study Completion Date: December 31, 2020

Arms and Interventions

Arm	Intervention/treatment
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; Other Name: marijuana
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; Other Name: marijuana
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; Other Name: marijuana

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. 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)
5. 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
6. 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)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Brook L Henry, PhD; (619) 543-4737; blhenry@ucsd.edu

Contact: Recruitment Office; hnrprecruitment@ucsd.edu

Locations

United States, California

UC Center for Medicinal Cannabis Research, UC San Diego; Recruiting

San Diego, California, United States, 92103

Contact: Brook L Henry, PhD 619-543-4737 blhenry@ucsd.edu

Principal Investigator: Brook L Henry, PhD

Sub-Investigator: Ron O Ellis, MD, PhD

Sub-Investigator: David Grelotti, MD

Sponsors and Collaborators

University of California, San Diego

Investigators

• Principal Investigator: Brook L Henry, PhD; University of California, San Diego

More Information

• Responsible Party: Brook Henry, Assistant Research Scientist, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT03099005 History of Changes
• Other Study ID Numbers: 170510
• First Posted: April 4, 2017
• Last Update Posted: October 18, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The principal investigator, Brook Henry PhD (blhenry@ucsd.edu), will supply individual participant data to other researchers after the project is completed.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Brook Henry, University of California, San Diego:

neuropathic pain; human immunovirus; vaporized cannabis

Additional relevant MeSH terms:

Neuralgia; Marijuana Abuse; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders