Azithromycin is an antibiotic which has been available since 1988, and is widely prescribed, with a good safety record. Antibiotics are effective in curing bacterial diseases, but not viral diseases. This trial is the first I've covered where an antibiotic was tested to treat, prevent, or cure type-1 diabetes, so it represents a new treatment path.
Why Azithromycin?
There are several different theories about what causes type-1 diabetes, one of which is that bacteria moving from the duodenum to the pancreatic duct causes type-1 diabetes. The duodenum is the part of the small intestine closest to the stomach. This is one of the "stomach flora" or "gut bacteria" theories which have been in the news recently.
If the cause is bad bacteria in the pancreatic duct, then (these researchers theorize), maybe the cure is to give the patient a dose of antibiotics to kill the bacteria, extra insulin to lower the stress on the remaining beta cells, and dietary guidance to prevent excess bacteria from moving from the duodenum to the pancreatic duct in the future. All this would be done very quickly after diagnoses of type-1 diabetes. That is the quick summary of the rationale behind this clinical trial.
This Clinical Trial
This trial is called the "Azithromycin Insulin Diet Intervention Trial in Type 1 Diabetes (AIDIT)" to include all three of the interventions being used. This trial will enroll people between 6 and 16 years old, who have been diagnosed within the last 10 days, so only "just diagnosed" people can participate.
The plan is to recruit 60 people, half of whom will get the treatment, and half will not. The study is not blinded. It started in Sept-2018 and they expect to finish in Dec-2021.
People will get three doses of Azithromycin per week, which is based on a protocol which has been used for years to treat people with cystic fibrosis. On a monthly basis, they will be given extra insulin via an IV, which is designed to give beta cells a rest and help them regrow. Finally, they will also be given dietary advice designed to have them drink less at meals, and eat meals more slowly, which is designed to prevent bacterial migration.
The study will run for a year, with C-peptide numbers being the primary end point. There are a total of 21 different secondary end points, including time within BG range, A1c, several measures of diet, quality of life, etc.
They are recruiting at one site in Sweden:
The Queen Silvia Children's Hospital / Sahlgrenska University Hospital, Gothenburg, Sweden
Contact: Gun Forsander
Contact: Olle Korsgren, MD, PhD +46176114187 olle.korsgren@igp.uu.se
Funding is from Barndiabetesfondens (Child Diabetes Foundation) in Sweden.
US Clincial Trial Record: https://clinicaltrials.gov/ct2/show/NCT03682640
EU Clinical Trial Record: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-002191-41/SE
Wikipedia: https://en.wikipedia.org/wiki/Azithromycin
Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.
7 comments:
Just wanna say thanks for all your work on this. I check this site every few months for any interesting news. Been a Type 1 since 2004.
The idea of using antibiotics for autoimmune diseases has been used for rheumatoid arthritis with success. A link between autoimmune diseases and chronic infections was shown for systemic lupus erythematosis According to an article by Alexandros P. Grammatikos and George C. Tsokos
Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosis
URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278563/ Autoimmunity in systemic lupus erythematosis is caused by a genetic mild immunodeficiency leading to acute infections becoming chronic which causes the immune system to start producing autoantibodies and they postulate that this mechanism may occur in other autoimmune diseases
There is general ignorance of chronic infections with obligate intracellular bacteria eg Lymes disease, Rickettsia, Qfever etc. These are treated with Doxycilin, macrolide antibiotics and quinoline antibiotics. The treatment takes years, depending on the the heaviness of the infection and of the person's immune status. It is also complicated by Herxheimer's reaction in which the dead bacteria release toxins making the patient feel very sick.
As I am a retired pathologist, I didn't have the contacts to initiate a study to show if treatment for these organisms would reverse Type 1 Diabetes
Although based on an inaccurate premise, the trial with Azithromycin may have some success, but it is likely that patients will opt out due to the Herxheimer effect
If this was found to be effective, could it be applied in the future to patients with a longstanding DM1? E.g. I know that pancreatic or beta cell transplants are problematic these days because the immune system will react to the new beta cells and destroy them after some time. Perhaps combining the transplant with this antibiotic treatment could prevent the immune system from further destroying the new beta cells in those patients?
It has been well demonstrated by Faustman and others that simply by ending the autoimmune attack on the beta cells of the pancreas will not in itself cause those cells to revive. Once dead, they are gone. Something else would have to stimulate re-growth, and various things, such as spleen cells and INGAP polypeptide have been tried, but so far, nothing works. Approaches such as the one reported here would, if successful, only slow or stop the autoimmune attack on beta cells when it first begins, in the hope that the patient can retain enough intact beta cells to produce sufficient insulin in the future to avoid outright diabetes, or to have a milder case, since it is known that patients with higher c-peptide levels indicative of remaining insulin production have an easier time controlling blood sugar. In itself, the approach discussed here would do nothing to help established cases, and would probably harm longstanding type 1 diabetics, since if new cases can be prevented, interest in curing established cases would fade. We would be medically stranded as the last victims of an historical disease.
Yes, I know that beta cells will not revive after the autoimmune attack is stopped.
However, some beta cell regrowth treatments are or could be unsuccessful because after the regrowth happens, those new beta cells would again be destroyed by the autoimmune system.
This is where this new study could be combined with such regrowth treatments to ensure that the new beta cells don't get killed, and it's why it could be useful for patients with established DM1.
For example, from https://cureresearch4type1diabetes.blogspot.com/2009/05/exsulin-new-phase-i-research-almost.html
"""The original developers of INGAP got back rights to it after P&G didn't like the phase-II results. Their analysis of the results convinced them that INGAP was helping grow new beta cells, but that those new cells were being killed off too quickly to help the patient. (Maybe because of the body's immune system, or maybe because of inflammation, or maybe for some other reason.)"""
If those new beta cells got killed because of the patient's immune system, then applying that INGAP treatment in combination with or after this antibiotic treatment could prevent those cells from getting killed, thus helping both new DM1 cases and old ones.
This is just some theoretical possibility and I'm not sure if it could be applied in real life (assuming all the assumptions became true, such as this "stop the autoimmune attack" treatments and the other "find a way to regrow or transplant beta cells" treatments were successful). Just some food for thought.
Every idea, however idiotic it may seem, must be tested. Many great discoveries have happened like this.
Many thousands of type 1 diabetics have had to take powerful immunosuppressive drugs for many years because of organ transplants, yet not one single instance of significant improvement in blood sugar control has ever been reported in such cases, with the obvious exception of pancreas transplants. From this we can assume that suppressing the autoimmune attack on the pancreatic beta cells will never, in itself, improve the diabetic state, unless we have a new-onset patient where a large number of intact beta cells remain to be saved.
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