Neuropeptide Therapy of Recent Onset Type 1 Diabetes

• Substance P (Drug)

Primary outcomes

• Stage A Safety: Side effects reported for entire cohort [Reported during the first 20-27 days following sP administration]: To determine if there are unexpected adverse events with intra arterial delivery of sP into the celiac artery in individuals with Type 1 Diabetes, and evidence of residual beta cell function as reflected by a peak C---peptide levels of > 200 pmol/L. Multiple measurements per patient will be aggregated to arrive at one reported value: Number of participants with abnormal laboratory values, adverse events and/or peak C-peptide levels >200pmol/L that are related to treatment.

Secondary outcomes

• C-Peptide Levels (small cohort) [Day 20-27 post sP injection]: To determine in an initial small cohort (n=12, toxicity and dose finding cohort) if one or more sP doses significantly increases the basal or stimulated c---Peptide levels at Day 20---27 post---injection using data from Mixed Meal Tolerance Test (MMTT).
• C-Peptide Levels (large cohort) [Day 20-27 post sP injection]: To assess in a larger cohort (n=40, continued safety and efficacy) whether sP dose, determined from the dose finding cohort, significantly increases basal or stimulated C-- peptide levels at Day 20---27 post sP---injection using MMTT data.

Other outcomes

• sP Longevity [3 and 6 months]: To determine an estimate of sP longevity in the entire cohort of patients, by monitoring HbA1c values, exogenous insulin requirement, daily recorded blood sugar levels and adverse event recording at 3 and 6 months post injection of sP. Multiple measurements per patient will be aggregated to arrive at one reported value for the aforementioned outcome measures.

Sex: All, ages: 10 Years to 18 Years

Inclusion Criteria:

* Recent onset T1D (CDA 2013 guidelines: See link in links section
* Age 10-18 years
* Disease Duration 3-30 months
* Fasting C-Peptide (measured at screening) greater than or equal to 33 pmol/L
* Post honeymoon phase based on the following criteria: History of HbA1c values and insulin requirements from diagnosis indicating a honeymoon period followed by increased insulin requirements which at time of recruitment are > 0.50 units/Kg together with an HbA1c value > 7.2 %; Patients with diabetes duration > 3 months who never experienced a honeymoon period as reflected by consistent HbA1c values > 7.2 % from the time of diagnosis and at the time of recruitment are using an insulin dose > 0.50 units/Kg.
* The presence of one or more of the TRPV1 alleles similar to those found in patients currently enrolled in the TRPV1-North American - European Study.
* Stimulated C-Peptide (measured at mixed meal tolerance at Stage A and Stage B of sP trial) ≥ 200 pmol/L and less than or equal to 1500 pmol/L.

Exclusion Criteria:

* Patients with known co-morbidities, including ACE-inhibitor treated hypertension as well as chromosomal abnormalities, involving one or more organ systems.
* Type 2 Diabetes Mellitus
* Patients with a known radiographic contrast allergy
* Pregnancy.

• Etienne Sochett, MD, Principal investigator, Hospital for Sick Children, Toronto Ontario