Neuropeptide Therapy of Recent Onset Type 1 Diabetes

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

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

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Substance P

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Holly Tschirhart; Phone Number: 204517 416-813-7654; Email: holly.tschirhart@sickkids.ca
• Study Contact Backup: Name: Catherine Pastor; Phone Number: 204396 416-813-7654

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Recruiting
      • Hospital For Sick Children
      • Contact: Holly Tschirhart; Phone Number: 204517 416-813-7654; Email: holly.tschirhart@sickkids.ca
      • Contact: Catherine Pastor; Phone Number: 204396 416-813-7654; Email: catherine.pastor@sickkids.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
sP Longevity	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.	3 and 6 months

Collaborators and Investigators

• Sponsor: Vanilloid Genetics Inc.
• Investigators: Principal Investigator: Etienne Sochett, MD, Hospital for Sick Children, Toronto Ontario

Publications and helpful links

Helpful Links

• CDA 2013 guidelines

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: May 19, 2016
• First Submitted That Met QC Criteria: June 28, 2016
• First Posted (Estimate): July 1, 2016

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 19, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Therapy; Neuropeptide; Onset
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Substance P; Neurokinin A
• Other Study ID Numbers: VanilloidGenetics-001-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes