Cannabidiol for the Treatment of Diabetic Peripheral Neuropathy: Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- DPN Pain Level
研究概览
简要总结
The "Cannabidiol for the Treatment of Diabetic Peripheral Neuropathy: Pilot study (CBD-DPN1)" is a double-blinded, placebo-controlled, crossover pilot study evaluating the efficacy of Cannabidiol (CBD) and full-spectrum CBD (fsCBD) tinctures in treating Diabetic Peripheral Neuropathy (DPN)-associated pain. DPN is a common, highly distressing complication of diabetes, characterized by chronic pain and loss of sensory function, for which currently available treatments primarily offer only symptomatic relief. CBD and fsCBD are being investigated for their potential neuroprotective and analgesic effects by regulating inflammation and oxidative stress.
The study aims to recruit 12 to 20 adult participants who have mild to moderate DPN. Subjects will receive either an active treatment (CBD isolate or fsCBD in MCT oil, dosed at 50 mg twice daily for a total of 100 mg daily) or a placebo during two sequential 6-week phases. The overall objective of this pilot phase is primarily methodological: to test and refine the clinical protocol, assess patient compliance and acceptability of the CBD formulations, and generate sufficient data to calculate the necessary sample size for a larger, definitive study. Efficacy will be measured using objective and subjective metrics, including DPN severity (DN4 Assessment Tool and DPNCheck™ for nerve conduction velocity) and pain level (PainDetect Questionnaire). Secondary outcomes include evaluating mood (HADS), sleep quality (MOS Sleep Scale), and quality of life (EQ-5D-5L).
详细描述
The Cannabidiol for the Treatment of Diabetic Peripheral Neuropathy: Pilot study (CBD-DPN1) is an interventional, double-blinded, placebo-controlled, crossover pilot study investigating the efficacy of cannabidiol (CBD) formulations in treating diabetic peripheral neuropathy (DPN)-associated pain. This study operates under an Investigational New Drug (IND) application cleared by the U.S. Food and Drug Administration (FDA).
Scientific Rationale and Objectives DPN is a widespread and highly distressing complication of Type 2 Diabetes (T2D), leading to chronic pain, numbness, and significant loss of quality of life. Current treatments primarily offer symptomatic relief without halting the disease progression. CBD is a non-psychoactive phytocannabinoid attracting attention for its neuroprotective action and potential therapeutic effect against DPN pain. Mechanistically, CBD is hypothesized to reduce neuropathic and musculoskeletal pain by regulating inflammation and oxidative stress through antagonism of CB1 receptors, agonism of CB2 receptors, and modulation of TRPV1 ion channels. Preclinical data further suggests CBD significantly improves behavioral DPN parameters in diabetic rat models and positively regulates mitochondrial homeostasis pathways (Nrf2-SIRT1 axis) in Schwann cells.
The overall objective is to determine the efficacy of CBD and Full-spectrum CBD delivered as a tincture in treating DPN-associated pain. As a pilot study, the primary objectives are methodological: to evaluate and refine the clinical protocol, assess patient compliance and acceptability of the CBD formulations, test organoleptic acceptability (if participants can discern active agent from placebo), and gather initial data necessary for power size estimates for a future large-scale study.
Study Design and Treatment Protocol The study targets the recruitment of approximately 30 subjects for screening, with a goal of enrolling a minimum of 12 to 20 adults with mild to moderate DPN. The total duration for each participant is about 4 months.
Crossover Design and Blinding: Participants are randomized into four treatment sequences, ensuring each subject receives both an active treatment phase and a placebo phase across the two sequential 6-week treatment periods (Phase I and Phase II). This design ensures that following the enrollment of 4, 8, 12, 16, or 20 participants, there is an equal distribution of subjects across the four treatment combinations. The study is double-blinded, meaning neither the subject nor the clinical investigators will know the assignment of the active agent or placebo during either phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult aged 40 to 70 years
- •Diagnosis of Type 2 Diabetes
- •Ambulatory and independently living adult
- •Minimum body weight of 50 kg (to ensure daily dose ≤2 mg/kg)
- •Physical exam completed within the previous 6 months
- •Liver Function Studies (ALT and AST) completed within the previous six months showing normal values
- •If NAFLD is present, ALT and AST levels are ≤2 times the Upper Limit of Normal (ULN)
- •DN4 questionnaire results indicate mild to moderate DPN
- •Nerve Conduction Test (NCT) confirms at least mild DPN
- •Signed ICF/Screening Consent
- •Able to complete required questionnaires (adequate vision)
排除标准
- •High-risk or severely ill individuals (e.g., high risk for general anesthesia, significant limitations due to heart/lung disease, ascites, renal failure, loss of limbs from diabetic complications)
- •Uncontrolled or severe cardiovascular disease (e.g., unstable angina, uncontrolled heart failure, recent myocardial infarction)
- •History of atrial fibrillation, dysrhythmias, MI within the previous 2 years, or stroke
- •Severe respiratory illness (e.g., uncontrolled asthma, COPD with frequent exacerbations, oxygen dependence)
- •Severe or uncontrolled liver disease (e.g., cirrhosis, active viral hepatitis A, B, or C, autoimmune hepatitis, uncontrolled primary biliary cholangitis or primary sclerosing cholangitis)
- •Elevation of liver enzymes (ALT or AST) exceeding 2 times the ULN, or bilirubin exceeding the ULN
- •Severe or uncontrolled kidney disease (e.g., end-stage renal disease requiring dialysis, uncontrolled nephrotic syndrome)
- •History of malignancy within the past 5 years (excluding certain low-risk non-melanoma skin cancers)
- •History of a seizure disorder
- •Blindness (poor vision preventing questionnaire completion)
- •Known allergy or previous adverse reaction to any ingredient, including natural strawberry flavoring
- •Reproductive Health (Women Only)
- •Currently pregnant or lactating
- •Women who can get pregnant who are not using acceptable methods of birth control
- •Current uncontrolled mental health conditions (e.g., major depressive episode with active suicidal ideation, bipolar disorder with current manic/hypomanic episode, or psychosis)
- •Diagnosis of a major depressive episode with active suicidal ideation and/or a plan to attempt suicide within the previous 5 years
- •Attempted suicide in the last 10 years
- •C-SSRS Suicide Ideation Subscore ≥5 at study onset
- •HADS-D score ≥15 at study onset
- •Used cannabis products in the past 30 days
- •Current use or history of illicit drug use or misuse of prescription medications within the previous 5 years
- •Heavy drinking (≥8 drinks/week for women; ≥15 drinks/week for men)
- •Taking medications that are known to cross-reacting with CBD or Cannabiods
研究组 & 干预措施
2. Placebo Phase 1 (CBD Isolate Phase 2)
Participants randomized to Arm 2 will be given a placebo tincture (0.5 ml twice daily for a total of 1 ml daily) for 6 weeks in Phase 1. After a 2-week washout period, they will be given the active tincture containing 100 mg of CBD isolate (100 mg/ ml) to use 0.5 ml twice daily for an additional 6 weeks. The bottles will be labeled: "TMH CBD for DPN Trial: (number) A" and "TMH CBD for DPN Trial: (number)B", where A refers to the vials to be used in phase one and B to the vials used for phase two. Since a vial contains a 30-day supply and each phase lasts 42 days, the participants will receive two identically labelled vials at the beginning of each phase.
干预措施: Placebo in MCT oil oral solution (Drug)
3. CBD Full-spectrum Phase 1 (Placebo Phase 2)
Participants randomized to Arm 3 will be given a Full-spectrum CBD isolate tincture with 100 mg of hemp-derived CBD isolate /ml (using 0.5 ml; 50 mg twice daily for a total of 100 mg daily) for 6 weeks in Phase 1. After a 2-week washout period they will be given an identical appearing placebo tincture for an additional 6 weeks. The bottles will be labeled: "TMH CBD for DPN Trial: (number) A" and "TMH CBD for DPN Trial: (number)B", where A refers to the vials to be used in phase one and B to the vials used for phase two. Since a vial contains a 30-day supply and each phase lasts 42 days, the participants will receive two identically labelled vials at the beginning of each phase.
干预措施: Full-Spectrum CBD hemp extract oral solution (Drug)
4. Placebo Phase 1 (CBD Full-spectrum Phase 2)
Participants randomized to Arm 4 will be given a placebo tincture (0.5 ml twice daily for a total of 1 ml daily) for 6 weeks in Phase 1. After a 2-week washout period, they will be given the active tincture containing 100 mg of CBD Full-spectrum isolate (100 mg/ ml) to use 0.5 ml twice daily for an additional 6 weeks. The bottles will be labeled: "TMH CBD for DPN Trial: (number) A" and "TMH CBD for DPN Trial: (number)B", where A refers to the vials to be used in phase one and B to the vials used for phase two. Since a vial contains a 30-day supply and each phase lasts 42 days, the participants will receive two identically labelled vials at the beginning of each phase.
干预措施: Placebo in MCT oil oral solution (Drug)
1. CBD Isolate Phase 1 (Placebo Phase 2)
Participants randomized to Arm 1 will be given CBD Isolate tincture 100 mg/ml (50 mg twice daily for a total of 100 mg daily) for 6 weeks in Phase 1. After a 2-week washout period they will be given an identical appearing placebo tincture for an additional 6 weeks. The bottles will be labeled: "TMH CBD for DPN Trial: (number) A" and "TMH CBD for DPN Trial: (number)B", where A refers to the vials to be used in phase one and B to the vials used for phase two. Since a vial contains a 30-day supply and each phase lasts 42 days, the participants will receive two identically labelled vials at the beginning of each phase.1
干预措施: Cannabidiol (CBD) oral solution (Drug)
结局指标
主要结局
DPN Pain Level
时间窗: Baseline (Day 0), Day 7, Day 21 (at home by subject), Day 35 (at home by subject), End of Phase I (Day 49), Day 63 (at home by subject), Day 77 (at home by subject), End of Phase II (Day 105).
Pain level will be assessed using the slightly modified "PainDETECT" Questionnaire. This instrument rates subjective pain 0 - 10 (zero no pain, 10 the worst) for current, average and worst over the last 4 weeks. It additionally scores neuropathic symptoms on a scale of zero to 35, with zero being no symptoms to 35 being the worst.
Diabetic peripheral neuropathy diagnosis
时间窗: Baseline Screening (Day 0)
DPN severity will be assessed using the DN4 Assessment Tool (including a clinical assessment of hypoesthesia and allodynia). The DN4 tool consists of 10 items across four sections, including both patient interview questions and a physical examination. Each "yes" answer receives 1 point, and each "no" answer receives 0 points. The points from all 10 items are summed to get a total score ranging from a minimum of 0 to a maximum of 10. A total score of 4 or more (≥4) suggests the presence of neuropathic pain. A score of 3 or below indicates that neuropathic pain is unlikely. A higher score is associated with worse DPN.
Diabetic Neuropathy Severity
时间窗: Baseline, End of Phase I (Day 49) (for NCT), End of Phase II (Day 91) (for NCT).
The DPNCheck™ instrument will be used to assess sural nerve conduction velocity (NCV) and sensory nerve action potential (SNAP) amplitude. Amplitude, The typical normal ranges are \> 40 m/s for SNAV and \> 4 µV SNAP, though values vary by study; lower values indicate worse neuropathy severity, with thresholds like \\(\<40\\) m/s for SNCV and \\(\<5\\) µV (or even \\(\<4\\) µV) for SNAP signaling mild-to-moderate damage, while amplitudes below 1.5 µV may register as zero due to device limits. Device Limitation: Values below 1.5 µV may be registered as 0 µV. Mild DPN: May show delayed SNCV (\< 40 m/s) or low amplitude. Moderate DPN: Often characterized by reduced SNAP amplitude (e.g., \< 5 µV). Severe DPN: Significant decreases in both amplitude and velocity, with very low or undetectable signals
次要结局
- Sleep Quality(Periodically over the approximately 4 month study duration)
- Mood and Depression(Periodically over the approximately 4 month study duration)
- Quality of Life Index(Periodically over the approximately 4-month study duration)
- Patient Compliance(End of Phase I (Day 49) End of Phase II (Day 105))
- Liver Function Monitoring (Safety Measure)(Baseline, (if previous results are > 3 months old), End of Phase II (Day 105))