Neuropeptide Therapy of Recent Onset 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

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if delivering a natural body chemical called substance P to a major artery can help people recently diagnosed with type 1 diabetes. The goal is to reduce inflammation and support the pancreas in managing blood sugar levels better.

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.

What safety data exists for Substance P treatment in humans?

The available research highlights that adverse event (AE) reporting in clinical trials, including those for pain treatments, is often inadequate. This means that while some safety data might exist, it may not be comprehensive or detailed enough to fully understand the safety of treatments like Substance P. ^{1 2 3 4 5}

How does the drug Substance P differ from other treatments for depression?

Substance P is unique because it acts as a neurotransmitter and neuromodulator, influencing mood by interacting with the neurokinin-1 receptor, which is different from traditional antidepressants that typically target serotonin or norepinephrine pathways. This mechanism may result in fewer sexual side effects compared to some standard antidepressants. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Substance P?

Research suggests that blocking Substance P with certain drugs can help reduce symptoms of major depression and anxiety, showing promise as a treatment for these conditions. ^{6 8 11 12 13}

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

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]

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]

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]

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]

Citations

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

Serum Substance P Concentration in Children With Traumatic Brain Injury: A First Report. [2021]

2. England pubmed.ncbi.nlm.nih.gov

The role of substance P in depression: therapeutic implications. [2021]

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

Substance P and Substance P receptor antagonists in the pathogenesis and treatment of affective disorders. [2022]

4. Norway pubmed.ncbi.nlm.nih.gov

Influence of tropisetron on the serum substance P levels in fibromyalgia patients. [2019]

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

Substance P serum levels are increased in major depression: preliminary results. [2022]

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

Adverse Event Reporting in Clinical Trials of Intravenous and Invasive Pain Treatments: An ACTTION Systematic Review. [2018]

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

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. [2022]

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

Adverse event reporting in nonpharmacologic, noninterventional pain clinical trials: ACTTION systematic review. [2018]

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

Substance P as a novel anti-obesity target. [2021]

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

Immunomodulation by tachykinin neuropeptides. [2019]

13. France pubmed.ncbi.nlm.nih.gov

[Substance P]. [2006]