Substance P for Type 1 Diabetes

Overseen By Holly Tschirhart

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Vanilloid Genetics Inc.

Must not be taking: ACE inhibitors

Disqualifiers: Type 2 diabetes, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Single treatment

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals recently diagnosed with type 1 diabetes. Researchers are testing how Substance P, a neuropeptide administered in varying doses directly to a major artery, might help manage the condition. They seek participants who have had type 1 diabetes for 3 to 30 months and are experiencing increasing insulin needs after an initial period of lower insulin use. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

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

Research has shown that substance P has been studied in various medical areas, often related to pain relief. Although detailed safety information about its use for type 1 diabetes is lacking, studies on similar treatments, such as celiac plexus block, suggest these methods are generally safe for managing chronic pain. People usually tolerate these procedures well, and they often help reduce pain.

In this trial, researchers administer substance P in different doses directly into the celiac artery. As an early-phase study, the main goal is to ensure safety and determine the best dosage. Early-phase trials primarily test the safety of a new treatment in humans, so researchers closely monitor participants for any side effects.

While specific data for substance P in type 1 diabetes is limited, its use in related treatments provides some reassurance about its potential safety. However, as with any new treatment, risks may exist, and this trial is an important step in understanding them better. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for type 1 diabetes, which often involve regular insulin injections, Substance P offers a novel approach by targeting the celiac artery with a single treatment. Researchers are excited about this treatment because Substance P is a neuropeptide that may help preserve or regenerate insulin-producing cells in the pancreas, addressing the root cause of the disease rather than just managing symptoms. With different doses being explored, from 1nmol/kg to 45nmol/kg, there's potential to fine-tune its effectiveness and safety. This innovative method could lead to fewer daily interventions and a significant improvement in quality of life for patients.

What evidence suggests that this trial's treatments could be effective for recent onset type 1 diabetes?

Research suggests that substance P might help treat newly diagnosed type 1 diabetes. Substance P, a small protein, aids nerve communication. It has increased blood flow in certain areas, potentially aiding healing or reducing inflammation. Studies have shown that when introduced into the body, substance P affects the celiac artery, which supplies blood to the pancreas. This is significant because the pancreas produces insulin, a key hormone for controlling blood sugar. Although more research is needed to understand substance P's direct effect on diabetes, its ability to improve blood flow and reduce inflammation offers hope for potential benefits. Participants in this trial will receive different dosages of substance P to evaluate its effects. ^{1 6 7 8 9}

Who Is on the Research Team?

Etienne Sochett, MD

Principal Investigator

Hospital for Sick Children, Toronto Ontario

Are You a Good Fit for This Trial?

Inclusion Criteria

Recent onset T1D (CDA 2013 guidelines: See link in links section

Disease Duration 3-30 months

Fasting C-Peptide (measured at screening) greater than or equal to 33 pmol/L

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intra-celiac artery injection of Substance P at varying doses (1nmol/kg, 5nmol/kg, 15nmol/kg, 45nmol/kg)

Single treatment

Follow-up

Participants are monitored for safety and effectiveness, including HbA1c values, exogenous insulin requirement, and adverse events at 3 and 6 months post-injection

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Substance P

How Is the Trial Designed?

Group I: Substance P - 5nmol/kg Experimental Treatment 1 Intervention

Substance P 5nmol/kg intra-celiac artery, single treatment

Group II: Substance P - 45nmol/kg Experimental Treatment 1 Intervention

Substance P 45nmol/kg intra-celiac artery, single treatment

Group III: Substance P - 1nmol/kg Experimental Treatment 1 Intervention

Substance P 1nmol/kg intra-celiac artery, single treatment

Group IV: Substance P - 15nmol/kg Experimental Treatment 1 Intervention

Substance P 15nmol/kg intra-celiac artery, single treatment

Who Is Running the Clinical Trial?

Vanilloid Genetics Inc.

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

A systematic review of adverse event (AE) reporting in clinical trials of intravenous and invasive pain treatments revealed no significant improvement in reporting quality since the 2004 CONSORT guidelines, with only 5 out of 10 reporting standards met on average.

Overall, 8% of the articles reviewed did not report any AE information, highlighting a critical need for better transparency and adherence to reporting standards in clinical trials to fully understand the risks associated with pain treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Event Reporting in Clinical Trials of Intravenous and Invasive Pain Treatments: An ACTTION Systematic Review. Williams, MR., McKeown, A., Pressman, Z., et al.[2018]

Adverse events (AEs) are reported in 49.1% of trial participants in placebo groups, indicating that these events are quite common and not solely due to the natural progression of conditions.

The prevalence of AEs in placebo groups (6.51%) is higher than in untreated groups (4.25%), suggesting that the nocebo effect may play a significant role in the experience of AEs during clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Howick, J., Webster, R., Kirby, N., et al.[2022]

A systematic review of nonpharmacologic pain treatment trials revealed significant inadequacies in adverse event (AE) reporting, with less than half of the trials detailing specific AE assessment methods.

AE reporting was more comprehensive in trials involving patients compared to those with healthy volunteers, indicating a need for improved adherence to reporting guidelines across all types of trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event reporting in nonpharmacologic, noninterventional pain clinical trials: ACTTION systematic review. Hunsinger, M., Smith, SM., Rothstein, D., et al.[2018]

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02820558

Neuropeptide Therapy of Recent Onset Type 1 Diabetes This study evaluates the delivery of substance P via the celiac artery in the treatment of recent onset type 1 diabetes. Official Title. A Phase I Study of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16769810/

Local disruption of the celiac ganglion inhibits substance P ... RTX treatment and ganglionectomy significantly reduced pancreatic edema by 46% (P < 0.001) and NK-1R internalization by 80% and 51% (P < 0.001 and P < 0.05, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10696325/

Efficacy and Safety of Celiac Plexus Neurolysis in the ... Celiac plexus neurolysis for the treatment of severe chronic pain secondary to oncological pathology in the upper hemiabdomen produces similar pain relief

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/7509333/

Substance P increases cochlear blood flow without ... Carotid artery infusions of substance P yielded reductions in systemic blood pressure and elevations in cochlear blood flow (CoBF), measured via laser ...

5. researchgate.net researchgate.net/publication/277566485_Evaluation_of_the_Efficacy_of_Intra-Operative_Celiac_Plexus_Block_on_Post-Operative_Analgesia_Stress_Response_Gut_Motility_and_Pulmonary_Function_in_Upper_Abdominal_Surgery_A_Double-Blind_Randomized_S

Evaluation of the Efficacy of Intra-Operative Celiac Plexus ... Evaluation of the Efficacy of Intra-Operative Celiac Plexus Block on Post-Operative Analgesia, Stress Response, Gut Motility and Pulmonary ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5730442/

Celiac Plexus Block and Neurolysis in the Management of ... Celiac plexus block and neurolysis are safe and effective procedures for managing chronic upper abdominal pain resulting from both malignant and benign disease.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/217899Orig1s000IntegratedR.pdf

217899Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov The available safety data show that seladelpar is safe for its intended use. Common adverse reactions include headache, gastrointestinal ...

8. msrads.web.unc.edu msrads.web.unc.edu/wp-content/uploads/sites/15695/2021/04/CPB-block-JVIR.pdf

Response To Celiac Plexus Block ... Celiac plexus neurolysis with ethanol or phenol was not offered due to lack of safety data for this patient population. After recovery from ...

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/pdf/10.1002/cnr2.1265

A retrospective case series of patients who ... Methods and Results: We conducted a retrospective case series of all patients with cancer who underwent CPB at 4 Sydney teaching hospitals from ...