Cannabis Derivatives for Diabetic Neuropathy

Recruiting at 3 trial locations

Overseen By Courtney C DiCocco

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Cannabis, Opioids

Disqualifiers: Cannabis use disorder, Psychiatric disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if cannabis derivatives, such as CBD (Epidiolex) and THC, can reduce chronic neuropathic pain in Veterans who haven't found relief with other treatments. Researchers are testing three treatments: CBD alone, a mix of THC and CBD (Nabiximols), and THC alone, with a placebo for comparison. Veterans with persistent pain that affects daily life and experience pain from normally non-painful stimuli (like a light touch) might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not change your current pain medications by more than 20% from 4 weeks before the screening until the study ends. So, you can continue your current medications as long as they remain stable.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cannabis compounds like CBD, THC, and a mix of THC + CBD have been studied for their safety in treating diabetic neuropathy, a type of nerve pain. These treatments are generally well-tolerated by patients.

For CBD (Epidolex), studies have examined its safety for treating diabetic nerve pain. Although specific details from these studies aren't provided here, the FDA has approved CBD for other conditions, indicating a known safety profile.

Regarding THC (Dronabinol), studies have not found significant negative effects, but more research is needed to confirm its safety specifically for nerve pain.

The combination of THC + CBD (Nabiximols) has demonstrated a good safety profile, with only 10% of people experiencing mild side effects, suggesting it is generally well-tolerated.

This trial is in an early phase, so researchers are closely monitoring safety, but previous research offers a hopeful view of these treatments' safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for diabetic neuropathy because they explore cannabis derivatives in a way that's different from traditional options. Unlike typical medications that primarily focus on pain relief through opioids or antidepressants, these treatments use CBD and THC, which may offer pain relief by targeting the body's endocannabinoid system. CBD (Epidolex), with a hefty 800 mg daily dose, aims to provide therapeutic effects without the psychoactive "high." THC + CBD (Nabiximols) combines both cannabinoids, potentially offering balanced relief with doses of 10.8 mg THC and 10 mg CBD daily. Lastly, THC (Syndros) focuses on delivering a target dose of 10 mg per day to harness THC's pain-relieving properties. These treatments are intriguing because they might offer effective relief with a different mechanism of action than current standard therapies.

What evidence suggests that this trial's treatments could be effective for diabetic neuropathy?

Research has shown that cannabis compounds might help with diabetic nerve pain. In this trial, participants may receive different cannabis-based treatments. Cannabidiol (CBD), a potential treatment in this trial, has significantly improved pain levels in people with diabetic nerve damage, according to several studies. THC, another cannabis compound and treatment option in this trial, has proven more effective in reducing sudden pain compared to placebo treatments. Products that combine THC and CBD, such as Nabiximols, are also being tested in this trial and have effectively relieved nerve pain symptoms in other studies. Overall, cannabis compounds have consistently reduced nerve pain, making them a promising option for managing diabetic nerve pain. ^{1 6 7 8 9}

Who Is on the Research Team?

Deepak D'Souza, MD MBBS

Principal Investigator

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Donald McGeary, PhD

Principal Investigator

South Texas Health Care System, San Antonio, TX

Are You a Good Fit for This Trial?

This trial is for Veterans aged 21+ with diabetic neuropathic pain who can consent to participate. They must have allodynia, meet NEURODIAB criteria for painful diabetic peripheral neuropathy, and experience persistent high-impact pain. Excluded are federal employees, those needing psychiatric hospitalization, pregnant or breastfeeding women, individuals using cannabis products or with a recent history of Cannabis Use Disorder.

Inclusion Criteria

You experience pain when touched lightly with a brush during a screening test.

I experience constant, severe pain.

I am a veteran aged 21 or older.

Exclusion Criteria

You need to be hospitalized for psychiatric reasons right away.

You have been diagnosed with Cannabis Use Disorder in the past 6 months according to DSM-5.

Unwilling to refrain from using cannabis or cannabis-based products through the entire duration of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cannabis derivatives (THC, CBD, or THC+CBD) or placebo to assess efficacy in reducing neuropathic pain

8 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CBD (Epidolex)
• Placebo
• THC + CBD (Nabiximols)
• THC (Dronabinol)

Trial Overview The study tests the effects of THC (Dronabinol), CBD (Epidolex), their combination (Nabiximols), and placebo on chronic diabetic neuropathic pain in Veterans. It's a phase II trial with four groups randomly assigned in a double-blind manner to determine potential benefits and adverse effects.

How Is the Trial Designed?

Group I: THC (Syndros) Active Control 2 Interventions

Target dose of 10mg per day.

Group II: CBD (Epidolex) Active Control 2 Interventions

Target dose of 800 mg per day.

Group III: THC + CBD (Nabiximols) Active Control 2 Interventions

Target dose of 10.8 mg / 10 mg per day.

Group IV: Placebo Placebo Group 1 Intervention

Identical in appearance to the three active comparators.

CBD (Epidolex) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Tuberous sclerosis complex-associated seizures

Approved in European Union as Epidyolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Tuberous sclerosis complex-associated seizures

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Cannabinoids, particularly nabiximols and Epidiolex®, have shown significant therapeutic benefits for conditions like chronic pain, spasticity in multiple sclerosis, and refractory epilepsy, indicating their potential as effective medical treatments.

Pharmaceutical companies are focusing on non-smokable delivery methods for cannabinoids to ensure consistent dosing and targeted effects, which could enhance their efficacy in treating various chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine. Urits, I., Borchart, M., Hasegawa, M., et al.[2020]

In a 38-week study involving 380 patients with peripheral neuropathic pain (PNP), the THC/CBD oromucosal spray significantly reduced pain severity, with average scores dropping from 6.9 to 4.2 on a 0-10 scale, and over half of the patients reported at least a 30% improvement in pain.

The THC/CBD spray was well tolerated over the study duration, with no new safety concerns and no increase in dosage sought by patients, indicating its long-term safety and efficacy in managing PNP associated with diabetes or allodynia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain. Hoggart, B., Ratcliffe, S., Ehler, E., et al.[2021]

In a study of 12 multiple sclerosis patients treated with nabiximols (Sativex®), 58.3% showed a significant reduction in spasticity, indicating its potential efficacy in managing MS-related symptoms.

Functional MRI analysis revealed that nabiximols treatment was linked to increased global brain connectivity, particularly in responders, and changes in connectivity in motor areas and the cerebellum, suggesting a possible mechanism of action for its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resting-state functional connectivity in multiple sclerosis patients receiving nabiximols for spasticity. Gajofatto, A., Cardobi, N., Gobbin, F., et al.[2023]

In a randomized controlled trial with 30 subjects, Sativex, a cannabis-based extract, did not show significant efficacy compared to placebo in reducing pain scores for painful diabetic peripheral neuropathy (DPN).

Both groups experienced improvements in pain, but the lack of significant differences suggests that Sativex may not provide additional benefits, and the presence of depression in patients could influence pain outcomes in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Selvarajah, D., Gandhi, R., Emery, CJ., et al.[2021]

Sativex, a cannabis-based oromucosal spray containing THC and CBD in a 1:1 ratio, has shown significant effectiveness in reducing neuropathic pain and other symptoms like spasticity in patients with multiple sclerosis, based on five randomized controlled trials involving 368 patients.

While Sativex is effective for managing certain neurological symptoms, common side effects include dizziness, sleepiness, and fatigue, and the long-term safety and potential for dependence remain uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sativex for the management of multiple sclerosis symptoms. Perras C, .[2016]

KLS-13019, a structural analogue of CBD, not only prevented the development of chemotherapy-induced mechanical sensitivity in mice but also effectively reversed established sensitivity, unlike CBD.

KLS-13019 showed potential in reducing reinforcing behaviors related to food and morphine, indicating it may have unique therapeutic benefits compared to CBD, which did not exhibit this effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioural and pharmacological effects of cannabidiol (CBD) and the cannabidiol analogue KLS-13019 in mouse models of pain and reinforcement. Foss, JD., Farkas, DJ., Huynh, LM., et al.[2021]

The combination of synthetic cannabidiol (CBD) and tetrahydrocannabivarin (THCV) significantly improved symptoms of paclitaxel-induced peripheral neuropathy in mice, showing a twofold enhancement in neurobehavioral outcomes compared to individual treatments.

This combination therapy effectively reversed harmful changes in protein expression caused by paclitaxel, suggesting a protective mechanism that involves the 5-HT1A and CB1 receptors, which are crucial for neuronal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents. Kumar Kalvala, A., Bagde, A., Arthur, P., et al.[2023]

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in the form of Sativex has shown therapeutic effects on refractory spasticity, central neuropathic pain, and bladder dysfunction in multiple sclerosis patients, addressing common symptoms that current oral medications struggle to effectively manage.

The use of THC/CBD is generally well-tolerated, with most adverse effects being mild to moderate, and a low rate of discontinuation suggests good long-term safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the tolerability and efficacy of Sativex in multiple sclerosis. Moreno Torres, I., Sanchez, AJ., Garcia-Merino, A.[2017]

In a study of 297 patients with moderate to severe MS-related spasticity, nabiximols (Sativex) demonstrated significant effectiveness, with a mean reduction in spasticity scores from 7.6 to 5.5 over 12 weeks.

Patients undergoing physiotherapy alongside nabiximols treatment had a higher likelihood of achieving clinically relevant improvement and were less likely to discontinue treatment, indicating that combining PT with nabiximols may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of physiotherapy intervention on patients with multiple sclerosis-related spasticity treated with nabiximols (THC:CBD oromucosal spray). Grimaldi, AE., De Giglio, L., Haggiag, S., et al.[2020]

A retrospective study involving 34 pediatric patients showed that nabiximols, a cannabinoid buccal spray, was primarily used to treat pain and nausea/vomiting, with a median treatment duration of 3.8 days.

Half of the patients reported perceived effectiveness, but the most common side effects were drowsiness and tachycardia in 9% of cases, highlighting the need for further research to establish the safety and efficacy of nabiximols in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing the Use of Nabiximols (Δ9-Tetrahydrocannabinol-Cannabidiol) Buccal Spray in Pediatric Patients. Hagg, L., Leung, S., Carr, R.[2023]

Citations

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Efficacy and Safety of Transdermal Medical Cannabis ... This novel transdermal medical cannabis formulation (THC:CBD:CBN) demonstrated significant therapeutic efficacy in ameliorating painful DPN symptoms while ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07162454

Effectiveness of CBD for Neuropathic Pain in Diabetic Foot ... Evaluation of cannabidiol and urea 10%. This study evaluated the impact of cannabidiol on neuropathic pain and the action of urea 10% on skin ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S036350232400474X

The Use of Cannabinoids in the Treatment of Peripheral ... Thirteen of 14 studies (79%) observed a statistically significant decrease in neuropathic pain score following treatment with a cannabinoid. Meta-analysis ...

4. mdpi.com mdpi.com/2227-9059/13/10/2406

Long-Term Efficacy and Safety of Inhaled Cannabis ... Research evidence demonstrates that THC and CBD, along with their natural cannabis source, produce pain relief effects when tested in diabetic pain models and ...

5. practicalneurology.com practicalneurology.com/news/sublingual-cannabidiol-tablet-shows-efficacy-for-treating-diabetic-peripheral-neuropathy-in-phase-2-trial/2469595/

Sublingual Cannabidiol Tablet Shows Efficacy for Treating ... Those treated with CBD had statistically and clinically significant improvements in average and highest pain scores compared with those treated ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12562105/

Long-Term Efficacy and Safety of Inhaled Cannabis Therapy ... Medical cannabis use leads to lower type 2 diabetes risk, along with better blood sugar management in patients, according to research ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04679545

Using Cannabidiol to Treat Diabetic Peripheral Neuropathy ... The primary objective of this study is: To evaluate the safety of PG-DN-20WS for the treatment of painful DPN of the feet compared to a placebo control, ...

8. mdpi.com mdpi.com/2218-273X/15/6/816

Are Cannabis-Based Medicines a Useful Treatment for ... Topically applied (transdermal) CBD oil demonstrated significant pain relief for patients with peripheral neuropathy of the lower extremities [52]. Sublingual ...

9. internationalcbc.com internationalcbc.com/transdermal-cannabis-mitigates-diabetic-neuropathy-in-clinical-trial/

Transdermal Cannabis Mitigates Diabetic Neuropathy In ... “GEE (Generalized Estimating Equation) analysis revealed significant pain amelioration at weeks 4, 8, and 12. The cannabis formulation exhibited ...