Dr. Jay Skyler is the chairman of Type 1 Diabetes Trialnet, an international network conducting clinical trials to prevent type 1 diabetes or interdict the type 1 diabetes disease process. Kaitlyn is involved in Trialnet. Dr. Skyler did a great job teaching in this session. It was one of the hardest for me because it reminds me not of what Andrew goes through every day, but what most likely lies ahead for Kaitlyn.
He went through the process: genetic predisposition, trigger, autoimmunity antibodies, loss of first phase insulin response only detectable by IVGTT, glucose intolerance detectable by oral glucose tolerance test (OGTT), and diabetes. Once you hit OGTT glucose intolerance or dysglycemia, you have a 75 - 80% chance of developing type 1 within the next five years. That counter started ticking for Kaitlyn in December 2008.
Last summer, when Kaitlyn's numbers came back so high (194 at 2 hours where >200 is diabetes), I did quite a bit of research on Teplizumab and Diamyd. I read medical journals & did my best to decipher what it all meant even though much of it was over my head. My conclusions, for what it's worth, was that teplizumab did have an effect in preserving c-peptide, but the idea of cytokine release scared me. Diamyd was safer, but didn't seem to have much effect. Well, in December of last year, both drugs failed their clinical trials. I wasn't that surprised about Diamyd, but Teplizumab? Others online asked, "How can a drug prove effective in phase 2 trials and fail miserably in phase 3?"
Dr. Skyler answered these questions. I've lost my notes on this section, but here is what I remember. Diamyd failed, plain and simple. Teplizumab on the other hand faced two problems. The first was a poor choice in endpoints. Every trial has to preselect how success will be measured. That trial defined success as A1Cs under 6.5 and using less than typical amounts of insulin. The average A1Cs were 7.1, which though still good fails by the endpoint. The best thing Teplizumab does is preserve c-peptide. C-peptide is a measure of how much insulin you make yourself. Studies show that c-peptide > .2 puts a patient at reduced risk for hypoglycemia as well as eye and kidney problems. So a new study with sustained c-peptide as the end point could be successful.
The second challenge of the Teplizumab trial came from the company & FDA themselves. They wanted to reduce the effects of the cytokine release - headache, nausea, and other flu-like symptoms. So they reduced the dosage (again, this is from memory, but I'm fairly certain) from 45 mg in the effective phase 2 study to ...wait for it... 3 mg. Guess what? 3 mg didn't do much.
Also interesting was Dr. Skyler's comments on the cytokine release symptoms. He didn't see them as side effects since it isn't anything permanent. It was an expected intolerance of the body to the drug and proof it was doing what it was supposed to. I talked to Dr. Skyler afterwards and told him about Kaitlyn and asked him if he had any safety concerns about teplizumab and whether or not he would allow his daughter to take it. He is convinced it is safe. They have seen it preserve c-peptide in newly diagnosed patients, and it is most effective in the subgroup of children and those closest to diagnosis. For example, it worked better on those 6 weeks from diagnosis than those 12 weeks after diagnosis. The hope is what if we could stop the autoimmune attack right now when she does nothing and her A1C is 4.8? That would be wonderful.
You might worry that Dr. Skyler would only tell me what I wanted to hear. He didn't. I shared with him last year's results to her OGTT, but how this year's were close to normal. It hurt when he looked me in the eye and said, "Yes, it can fluctuate. However, at this point, we would consider your daughter at a 80-95% risk of developing type 1 in the next five years." Ouch!
Whether or not to do teplizumab is a decision we will likely have to make. Trialnet is doing a study trying to prevent diabetes altogether using teplizumab on people like Kaitlyn. The FDA requires a phase in of ages. They have to prove safety in the 18 and up population before taking 12 and up, and then 8 and up. Dr. Skyler has already requested from the FDA to take the younger crowd. Once the FDA approves 12 and up, he says that Kaitlyn's name will automatically show up to be contacted. It is being offered at Vanderbilt.
Please pray with us that we will know what to do. I know the decision is probably coming, but I'm sure we will be blind-sided. It will require daily infusions for a two week period. It is hard to know what side effects are really out there. I'm not a fan of drugs, especially experimental ones. On the other hand, every story I've read has been positive. Some are still making c-peptide 9 years later! I would love Kaitlyn to be spared this horrible disease. She is doing well right now. She started and ended her last OGTT in range, but did hit 208 in between. Her A1C is 4.8. I think it is miraculous that she is doing as well as she is. I believe it is the restraining hand of God on her life. Please pray that it continues to be so!
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