Neuropeptide Therapy of Recent Onset Type 1 Diabetes

Study Overview
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Brief Summary
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This study evaluates the delivery of substance P via the celiac artery in the treatment of recent onset type 1 diabetes.

Official Title
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A Phase I Study of Safety and Pharmacological Activity of Substance P (sP) in the Reversal of Recent-Onset Type 1 Diabetes (T1D)

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Substance P


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Substance P - 1nmol/kg<br>Substance P 1nmol/kg intra-celiac artery, single treatment | Drug: Substance P<br> <br> |
| Experimental: Substance P - 5nmol/kg<br>Substance P 5nmol/kg intra-celiac artery, single treatment | Drug: Substance P<br> <br> |
| Experimental: Substance P - 15nmol/kg<br>Substance P 15nmol/kg intra-celiac artery, single treatment | Drug: Substance P<br> <br> |
| Experimental: Substance P - 45nmol/kg<br>Substance P 45nmol/kg intra-celiac artery, single treatment | Drug: Substance P<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage A Safety: Side effects reported for entire cohort | 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. | Reported during the first 20-27 days following sP administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-Peptide Levels (small cohort) | 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). | Day 20-27 post sP injection | 
| C-Peptide Levels (large cohort) | 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. | Day 20-27 post sP injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuropeptide, Therapy, Onset