YJ001 Spray for Diabetic Neuropathy

Overseen By Hainan Yue

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Zhejiang Hanmai Pharmaceutical Technology Co., Ltd.

Must be taking: Antidiabetic agents, Insulin

Must not be taking: Aspirin, Blood thinners

Disqualifiers: Asthma, Cardiovascular disease, Depression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 11 days

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that certain medications, like aspirin, salicylic acid products, and some herbal preparations, should not be used within 14 days before the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug YJ001 Spray for Diabetic Neuropathy?

The research on Centella asiatica triterpenes and a curcumin derivative called J147 shows that these compounds can improve symptoms of diabetic neuropathy by enhancing microcirculation and providing neuroprotective effects. These findings suggest that similar treatments might be effective for diabetic neuropathy. ^{1 2 3 4 5}

How does the YJ001 spray differ from other drugs for diabetic neuropathy?

The YJ001 spray is unique because it is administered as a spray, which may offer a more convenient and potentially faster-acting alternative compared to traditional oral medications or capsules used for diabetic neuropathy. ^{1 6 7 8 9}

What is the purpose of this trial?

This Phase I, randomized, double-blind and placebo controlled study is to evaluate the safety, tolerability, and PK, and to preliminarily assess the efficacy of topically administered YJ001 in a multiple-ascending dose (MAD) fashion in the patients with DPNP. The study will be conducted at a single study center. In this study, 2 cohorts (N=24, 12 subjects for each cohort), each cohort will consist of 10 active and 2 placebo, with approximately equal numbers of male and female subjects. Each subject will be administered a single dose of YJ001 as multiple sprays topically on both feet and below the ankle in the morning on Day 1 and Day 2, and will be administered as twice daily doses once in the morning and the other in the evening (with an interval of 11 to 13 h) from Day 3 through Day 11.

Research Team

Douglas Scott Denham

Principal Investigator

5430 Fredericksburg Rd, Suite 200, San Antonio Texas 78229

Eligibility Criteria

This trial is for individuals with diabetic peripheral neuropathic pain (DPNP). Participants should be able to apply a spray treatment on their feet and follow the study's schedule. Specific eligibility details are not provided, but typically include factors like age range, severity of DPNP, and overall health status.

Inclusion Criteria

Glycated hemoglobin (HbA1c) ≤ 10% at screening

Able and willing to comply with all study requirements

Subjects voluntarily consenting for participation in the study and having signed informed consent document

Exclusion Criteria

History of clinically significant drug, food allergy, skin allergy, or sensitivity to drugs of the same class or known hypersensitivity to YJ001 or any of its components

History of asthma (except resolved childhood asthma)

Positive test results for SARS-CoV-2 at Screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person)

Treatment

Participants receive multiple doses of YJ001 topically on both feet and below the ankle

11 days

Daily visits (in-clinic)

Safety and PK Evaluation

Safety and pharmacokinetics are evaluated, and dose escalation decisions are made

5 days

In-clinic monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 days

Telephone follow-up

Treatment Details

Interventions

• YJ001

Trial Overview The trial is testing YJ001, a new medication in spray form against a placebo spray. It's designed to see if it's safe and works for relieving nerve pain in diabetic patients. The test involves multiple doses over several days at one study center with both men and women participating equally.

Participant Groups

Group I: Cohort M2 (10 active, 2 placebo) Experimental Treatment 2 Interventions

414 mg/administration

Group II: Cohort M1 (10active, 2 placebo) Experimental Treatment 2 Interventions

296 mg/administration

Who Is Running the Clinical Trial?

Zhejiang Hanmai Pharmaceutical Technology Co., Ltd.

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

The meta-analysis of 8 studies involving 656 patients showed that Tongmai Jiangtang capsules (TJC) combined with conventional treatment significantly improved nerve conduction velocities in diabetic peripheral neuropathy (DPN) patients compared to conventional treatment alone.

No adverse drug reactions were reported with the use of TJC, indicating a favorable safety profile, but the authors caution that the results should be interpreted carefully due to significant variability in the data across studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Tongmai Jiangtang capsule combined with conventional therapy in the treatment of diabetic peripheral neuropathy: a systematic review and meta-analysis. Sun, LX., Li, YY., Xie, YM.[2023]

In a 52-week randomized, double-blind, placebo-controlled trial involving 43 Type II diabetic patients, the standardized extract of Centella asiatica (CAST) significantly reduced neuropathy symptoms, particularly in total symptom score and paresthesia, compared to placebo.

CAST was well tolerated and showed potential as a disease-modifying treatment for diabetic neuropathy, as it improved microcirculation and mirrored effective neurotropic concentrations observed in preclinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Centella asiatica triterpenes for diabetic neuropathy: a randomized, double-blind, placebo-controlled, pilot clinical study. Lou, JS., Dimitrova, DM., Murchison, C., et al.[2023]

The Yi-Qi-Huo-Xue-Tong-Luo formula (YQHXTLF) contains 86 active ingredients and targets 110 specific pathways related to diabetic peripheral neuropathy (DPN), suggesting a complex mechanism of action.

Key targets like TP53, MAPK1, JUN, and STAT3 are involved in critical pathways such as the AGE-RAGE signaling pathway and TNF signaling pathway, indicating that YQHXTLF may help regulate inflammation and cell survival in DPN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network Pharmacology and Molecular Docking Study on the Potential Mechanism of Yi-Qi-Huo-Xue-Tong-Luo Formula in Treating Diabetic Peripheral Neuropathy. Lin, Y., Shen, C., Wang, F., et al.[2022]

J147, a curcumin derivative, shows promise in treating diabetic neuropathy in a mouse model, effectively improving nerve function and reducing pain associated with diabetes-induced nerve damage.

The drug works by decreasing neuroinflammation and may activate the AMP kinase pathway, suggesting it could be a single-agent alternative to the multiple medications typically needed to address the various causes of diabetic neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel curcumin derivative for the treatment of diabetic neuropathy. Daugherty, DJ., Marquez, A., Calcutt, NA., et al.[2022]

DA 9801, a herbal medicine, shows potential in treating diabetic neuropathy by acting on mechanisms related to nerve growth factor (NGF), which is crucial for nerve regeneration.

Current treatments for diabetic neuropathy do not effectively address the underlying pathophysiological mechanisms, highlighting the need for innovative approaches like DA 9801 that target nerve regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel botanical drug for the treatment of diabetic neuropathy. Choi, SZ., Son, MW.[2011]

DDD-028 is a small molecule that not only relieves pain in diabetic neuropathy (DN) but also shows potential to address the underlying nerve damage, making it a promising disease-modifying treatment.

In rodent models of DN induced by streptozotocin, DDD-028 demonstrated significant pain relief and also reduced nerve damage, suggesting it could be more effective than current medications that only target pain symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DDD-028: A potent, neuroprotective, non-opioid compound for the treatment of diabetic neuropathy. Micheli, L., Rajamoni, J., Di Cesare Mannelli, L., et al.[2023]

NRD135S.E1 (NRD.E1) is a new oral medication developed for treating painful diabetic peripheral neuropathy, showing rapid absorption and good tolerability in three phase I studies involving healthy male and female subjects.

The studies demonstrated that NRD.E1's absorption is dose-dependent and increases when taken with food, with no significant accumulation in the body after daily doses, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Single-Ascending-Dose, Multiple-Dose, and Food Interaction Studies of NRD.E1, an Innovative Nonopioid Therapy for Painful Diabetic Peripheral Neuropathy. Tiecke, E., Rainisio, M., Guentert, T., et al.[2023]

Compound Qiying Granules (CQYG) significantly improved blood glucose levels and reduced nerve damage in diabetic peripheral neuropathy (DPN) models, indicating its potential as a therapeutic intervention.

CQYG demonstrated neuroprotective effects by inhibiting endoplasmic reticulum (ER) stress and apoptosis, as evidenced by changes in protein expression and improved nerve morphology in both rat and cell models of DPN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis. Hu, Y., Chen, C., Liang, Z., et al.[2023]

Bogijetong decoction (BGJTD) and its reconstituted subgroup, Be decoction (BeD), effectively reduced neuropathic pain in diabetic animals, as shown by decreased latency to thermal stimulation and improved neurite outgrowth in nerve cells.

Both BGJTD and BeD treatments modulated key biochemical pathways, increasing phospho-Erk1/2 levels while decreasing TNF-α production, indicating their potential mechanisms of action in alleviating diabetic neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective Effects of Bogijetong Decoction and Its Selected Formula on Neuropathic Insults in Streptozotocin-Induced Diabetic Animals. Kim, KJ., Namgung, U., Cho, CS.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Tongmai Jiangtang capsule combined with conventional therapy in the treatment of diabetic peripheral neuropathy: a systematic review and meta-analysis. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Centella asiatica triterpenes for diabetic neuropathy: a randomized, double-blind, placebo-controlled, pilot clinical study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Network Pharmacology and Molecular Docking Study on the Potential Mechanism of Yi-Qi-Huo-Xue-Tong-Luo Formula in Treating Diabetic Peripheral Neuropathy. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A novel curcumin derivative for the treatment of diabetic neuropathy. [2022]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Novel botanical drug for the treatment of diabetic neuropathy. [2011]

6. England pubmed.ncbi.nlm.nih.gov

DDD-028: A potent, neuroprotective, non-opioid compound for the treatment of diabetic neuropathy. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Single-Ascending-Dose, Multiple-Dose, and Food Interaction Studies of NRD.E1, an Innovative Nonopioid Therapy for Painful Diabetic Peripheral Neuropathy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Protective Effects of Bogijetong Decoction and Its Selected Formula on Neuropathic Insults in Streptozotocin-Induced Diabetic Animals. [2020]