Thursday, September 15, 2016

Substance P Starts a Phase-I Clinical Trial

Substance P is a peptide (a part of a protein) which is used by several different organs and for several different purposes.   Research done in the early 2000s found that a specific type of neuron (called "TRPV1(+) pancreatic sensory neurons") control islet inflammation and insulin resistance. Removing these neurons from NOD mice prevented diabetes from developing.  Injecting NOD mice with Substance P, which affects these neurons, cured diabetes.   This clinical trial will test this same treatment in people, rather than mice.

People who have followed type-1 diabetes research for a long time might remember the news stories that injecting capsaicin (the active ingredient in hot chilis) would cure type-1 diabetes.  They were first published in 2006 and get recycled every now and then.  (Usually as examples of the grand conspiracy to suppress type-1 cures, especially cheap, natural cures.)  Anyway, the idea that capsaicin would cure type-1 diabetes comes out of this same line of research in NOD mice.  Capsaicin and Substance P are different, but they affect the same neurons in the pancreas, and the researchers tested both and reported on both in the same journal article.  The clinical trial is Substance P only, no capsaicin.

The Study

This Phase-I trial will start out enrolling 12 kids (between 10 and 18 years old) and later expand to 40 kids.  They are looking for people who were diagnosed "recently" but have already passed through their honeymoon period.  Their definition of "done with the honeymoon" is needing to inject more than 1/2 a unit of insulin per kilogram of body weight per day.  

They are testing four different doses of Substance P.  So no one will get a placebo, everyone will get the treatment, just at different doses.  People will get a single intravenous dose of Substance P, and will be followed for 6 months.  The primary outcome for this study is safety (prevalence of side effects), while the secondary outcomes are measuring effectiveness (C-peptide, a surrogate for natural insulin production).

The study started in May 2016 and they hope to finish in September 2017 (I assume that is for the 12 person part of the study).

They are recruiting at one location in Canada: Hospital for Sick Children  Toronto, Ontario
Contact: Holly Tschirhart    416-813-7654 ext 204517
Contact: Catherine Pastor    416-813-7654 ext 204396

A Little History

The history of this research really brought home to me the slow pace of research in general.  Here is a brief timeline:

1990s Earliest research into Substance P and type-1 diabetes.
2000 People with type-1 diabetes have less Substance P.
2006 Publication of cure results in NOD mice.
2007 "We expect to begin intervention studies in 2008"
2016 Intervention studies actually start.

If you want a single golden example of why there is so much false hope that a cure for type-1 diabetes is just around the corner, read this article, originally published in 2006:
Note the last sentence:
"Dosch and Salter expect to complete human trials of the treatment in the next year."
But also consider the general level of optimism and simplicity in the news report.  But the truth was completely different.  Now, 10 years after this news article, the research is just starting clinical trials.

This is the first clinical trial run by this company, Vanilloid Genetics Inc, which was founded by Dr. Dosch (and others), one of the original researchers from the NOD mice work in 2006.

Clinical Trial Registry:

Joshua Levy
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.