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Post by fofos2000i on Jun 27, 2016 4:08:38 GMT -5
study 6/22
Improving Efficacy of Inhaled Technosphere Insulin (Afrezza) by Postmeal Dosing: In-silico Clinical Trial with the University of Virginia/Padova Type 1 Diabetes Simulatorwww.ncbi.nlm.nih.gov/pubmed/27333446Abstract
BACKGROUND: Technosphere® insulin (TI), an inhaled human insulin with a fast onset of action, provides a novel option for the control of prandial glucose. We used the University of Virginia (UVA)/Padova simulator to explore in-silico the potential benefit of different dosing regimens on postprandial glucose (PPG) control to support the design of further clinical trials. Tested dosing regimens included at-meal or postmeal dosing, or dosing before and after a meal (split dosing). METHODS:
Various dosing regimens of TI were compared among one another and to insulin lispro in 100 virtual type-1 patients. Individual doses were identified for each regimen following different titration rules. The resulting postprandial glucose profiles were analyzed to quantify efficacy and the risk for hypoglycemic events. RESULTS:
This approach allowed us to assess the benefit/risk for each TI dosing regimen and to compare results with simulations of insulin lispro. We identified a new titration rule for TI that could significantly improve the efficacy of treatment with TI.
CONCLUSION:In-silico clinical trials comparing the treatment effect of different dosing regimens with TI and of insulin lispro suggest that postmeal dosing or split dosing of TI, in combination with an appropriate titration rule, can achieve a superior postprandial glucose control while providing a lower risk for hypoglycemic events than conventional treatment with subcutaneously administered rapid-acting insulin products. |
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Post by sweedee79 on Jun 27, 2016 7:04:54 GMT -5
This is exactly what we need to see happening. Afrezza is not the same as lispro dose for dose even though the pkg insert that comes with Afrezza says it is. Nice to see these studies being done, it is encouraging.
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Post by oldfishtowner on Jun 27, 2016 8:00:49 GMT -5
Now all we need is a clinical trial to show the same.
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Post by johnhindepost on Jun 27, 2016 9:15:53 GMT -5
Link to Complete Orignal Article online.liebertpub.com/doi/pdf/10.1089/dia.2016.0128DIABETES TECHNOLOGY & THERAPEUTICS Volume 18, Number 9, 2016 Mary Ann Liebert, Inc. DOI: 10.1089/dia.2016.0128 ORIGINAL AR TICLE Improving Efficacy of Inhaled Technosphere Insulin (Afrezza) by Postmeal Dosing: In-silico Clinical Trial with the University of Virginia/Padova Type 1 Diabetes Simulator Roberto Visentin, PhD,1 Clemens Giegerich, MS,2 Robert Ja¨ger, PhD,2 Raphael Dahmen, MD,2 Anders Boss, MD,3 Marshall Grant, PhD,4 Chiara Dalla Man, PhD,1 Claudio Cobelli, PhD,1 and Thomas Klabunde, PhD2 |
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Post by agedhippie on Jun 27, 2016 9:55:37 GMT -5
This is exactly what we need to see happening. Afrezza is not the same as lispro dose for dose even though the pkg insert that comes with Afrezza says it is. Nice to see these studies being done, it is encouraging. It's not a real study, it's just a computer model so it will have no direct impact. What it does do that is useful is suggest parameter for subsequent real studies. |
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Post by brentie on Jun 27, 2016 9:58:11 GMT -5
Thanks, Johnhindepost , for finding that original article.
Most of it was Greek to me but this did stand out from the discussion section...
"Clinical studies are currently planned to validate the results from these
in-silico meal test simulations in T1D."
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Post by mnkdfann on Jun 27, 2016 12:32:15 GMT -5
Most of it was Greek to me but this did stand out from the discussion section..."Clinical studies are currently planned to validate the results from these
in-silico meal test simulations in T1D." That throwaway line doesn't necessarily mean much without more information. Researchers (myself included, though admittedly in a different area than these guys) often include lines like that. It is almost always conditional on future funding and resources. It may be included just to help convince a referee on the fence that the current research is more important than it may seem. It may also be included just to 'mark the territory'. |
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Post by peppy on Jun 27, 2016 12:41:59 GMT -5
Link to Complete Orignal Article online.liebertpub.com/doi/pdf/10.1089/dia.2016.0128DIABETES TECHNOLOGY & THERAPEUTICS Volume 18, Number 9, 2016 Mary Ann Liebert, Inc. DOI: 10.1089/dia.2016.0128 ORIGINAL AR TICLE Improving Efficacy of Inhaled Technosphere Insulin (Afrezza) by Postmeal Dosing: In-silico Clinical Trial with the University of Virginia/Padova Type 1 Diabetes Simulator Roberto Visentin, PhD,1 Clemens Giegerich, MS,2 Robert Ja¨ger, PhD,2 Raphael Dahmen, MD,2 Anders Boss, MD,3 Marshall Grant, PhD,4 Chiara Dalla Man, PhD,1 Claudio Cobelli, PhD,1 and Thomas Klabunde, PhD2 Than you for a look at the study. reading it and trying to comprehend the way the measurement was done, I wondered how this study using Type 1 Diabetes Simulator, comparing an insulin analogue lispro would account for the phase 1 insulin response users get from technosphere insulin afrezza and not subq insulin analogues. The quote from the study, they infused glucose to 160 mg/dl? Yes with a type 1 using analogues.
The dosages where difficult to understand if someone can explain them to me. In this study, 4 unit afrezza = 10 unit lispro. In the clamp studies, different study, 4 units afrezza equal to 3.1 unit lispro. Is this the difference in the phase 1 could not be measured in this stimulated study? Am I just way off in my understanding to bring this up. ??
Additionally from a thread sports posted from afrezza user, sam: Afrezzauser (afrezzauser)
6/27/16, 9:14 AM
Took 8u #afrezza 105min ago eating a decent size meal w @brendanphyland in London #bgnow still at 85.Probably do a 4u follow up.Will update
sam's; Afrezza phase 1 seems to have kept his glucose from going high in the first place. in the olden days when I learned the numbers, a normal blood glucose was 60 to 90. Now I hear hypoglycemia is 70mg/dl www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/hypoglycemia-low-blood.html
My comment, some of our people running their blood glucose so tight. Sam must really know himself and the meal to anticipate another 4 units. Afrezza seems to be the cat's meow.
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Post by agedhippie on Jun 27, 2016 13:49:04 GMT -5
It depends what you call a hypo. The first physiological change happens at 70 which is where the body stops putting out insulin and starts releasing glucagon. The second change is around 55-60 which is where the body starts to panic and dumps epinephrine to provoke the liver to dump glucose. Once you are below this point random parts of the brain become impaired - the random part is why sometimes you become incoherent immediately and other times you can be in the 20s before it's noticeable. There are differences between Type 1 and Type 2. Type 1 tend to lose the first phase glucagon response so they transition to second phase and the epinephrine dump much faster. The epinephrine response also kicks in at varying levels (55 to 60 is where it kicks in with non-diabetics) depending on where the average levels have been sitting. If you have been running high it can kick in much earlier, if you have been running low averages it kicks in much later which can cause hypo unwareness (a serious problem). |
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Post by dreamboatcruise on Jun 27, 2016 17:16:54 GMT -5
This is exactly what we need to see happening. Afrezza is not the same as lispro dose for dose even though the pkg insert that comes with Afrezza says it is. Nice to see these studies being done, it is encouraging. It's not a real study, it's just a computer model so it will have no direct impact. What it does do that is useful is suggest parameter for subsequent real studies. Individual doctors could choose to adopt titration techniques informed by these results. |
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Post by mnkdnut on Jun 28, 2016 2:06:56 GMT -5
Assuming it's accurate enough, this simulation capability is fantastic IMO for two reasons: 1.) it will help future clinical trial protocols be designed to get the very best results out of Afrezza (please, no more high drop-out rates and non-inferior results!), and 2.) it could make for an excellent teaching tool. Imagine a laptop or tablet based simulator tool that would allow a nurse educator or sales rep to walk a patient (or doctor) through various scenarios of meal types, dosing and dose timing. Patients could "get it" early on (what it truly means to harness fast-in and fast-out insulin), and not depend on being resilient enough and curious enough to figure it out - maybe - on their own. Bravo to whoever championed the idea of doing these simulations.
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Post by agedhippie on Jun 28, 2016 6:25:32 GMT -5
Assuming it's accurate enough, this simulation capability is fantastic IMO for two reasons: 1.) it will help future clinical trial protocols be designed to get the very best results out of Afrezza (please, no more high drop-out rates and non-inferior results!), and 2.) it could make for an excellent teaching tool. Imagine a laptop or tablet based simulator tool that would allow a nurse educator or sales rep to walk a patient (or doctor) through various scenarios of meal types, dosing and dose timing. Patients could "get it" early on (what it truly means to harness fast-in and fast-out insulin), and not depend on being resilient enough and curious enough to figure it out - maybe - on their own. Bravo to whoever championed the idea of doing these simulations. The key phrase is "Assuming it's accurate enough". Computer models like this are notoriously flaky because you are extrapolating a whole universe from a single point, in this case a standardized meal. Nobody would use this except for the broadest recommendations such as dose immediately after the meal. The value is in directing protocol for the next proper trial. |
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Post by dreamboatcruise on Jun 28, 2016 18:39:34 GMT -5
Assuming it's accurate enough, this simulation capability is fantastic IMO for two reasons: 1.) it will help future clinical trial protocols be designed to get the very best results out of Afrezza (please, no more high drop-out rates and non-inferior results!), and 2.) it could make for an excellent teaching tool. Imagine a laptop or tablet based simulator tool that would allow a nurse educator or sales rep to walk a patient (or doctor) through various scenarios of meal types, dosing and dose timing. Patients could "get it" early on (what it truly means to harness fast-in and fast-out insulin), and not depend on being resilient enough and curious enough to figure it out - maybe - on their own. Bravo to whoever championed the idea of doing these simulations. The key phrase is "Assuming it's accurate enough". Computer models like this are notoriously flaky because you are extrapolating a whole universe from a single point, in this case a standardized meal. Nobody would use this except for the broadest recommendations such as dose immediately after the meal. The value is in directing protocol for the next proper trial. I'm sure you are correct that this wouldn't be able to predict metabolic behavior of particular patients. Do you know that it uses a "standardized meal"? Doesn't seem like it would be too difficult to add in some basic model of digestion/absorption to broadly capture much of the variability across the population (perhaps missing some statistical outliers) and then allow various simulated meals (specified by size and nutritional content or by glycemic index) to be fed to the various simulated patients. |
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Post by agedhippie on Jun 28, 2016 20:34:18 GMT -5
The key phrase is "Assuming it's accurate enough". Computer models like this are notoriously flaky because you are extrapolating a whole universe from a single point, in this case a standardized meal. Nobody would use this except for the broadest recommendations such as dose immediately after the meal. The value is in directing protocol for the next proper trial. I'm sure you are correct that this wouldn't be able to predict metabolic behavior of particular patients. Do you know that it uses a "standardized meal"? Doesn't seem like it would be too difficult to add in some basic model of digestion/absorption to broadly capture much of the variability across the population (perhaps missing some statistical outliers) and then allow various simulated meals (specified by size and nutritional content or by glycemic index) to be fed to the various simulated patients. I went back and read the paper this time rather than just skim it! The algorithm used seems fairly robust, it's derived from the AP algorithms and FDA approved for modelling (but not for human use). The PK curve is taken from the NCT01544881 (MKC-TI-177) trial back in 2013 which set the PK curve for the Afrezza prescribing note. They then took individual variances within the trial data and used that to create a much large data set (the wonders of MATLAB). This gave them a 100 virtual humans based of the characteristics of the original 12 real people. They feed the 100 virtual humans an ISO standard 50g meal and that's where the results came from. As you correctly said this bypasses all the nasty real world issues. It is based on the clamp data and not real food. This is why you would not be wise to use it medically. It fails the pizza test! |
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Post by sweedee79 on Jun 28, 2016 23:36:39 GMT -5
This is exactly what we need to see happening. Afrezza is not the same as lispro dose for dose even though the pkg insert that comes with Afrezza says it is. Nice to see these studies being done, it is encouraging. It's not a real study, it's just a computer model so it will have no direct impact. What it does do that is useful is suggest parameter for subsequent real studies. You seem to want to poo poo on every parade.. hope that isn't the case.. perhaps you are just keeping it real which I guess is good... not sure.. but whether or not it is a simulated study or a clinical study it is still a study of sorts and will hopefully lead to relevant information that can be used for something... . I don't need the study I already know.. My dad is angry every day because he cant have his Afrezza.. basicly all part D plans have removed it from their formulary until 2017 ... and we cant ignore Sam Finta and others with the same amazing results... So I still say this is exactly what we need to see happening... it is a start and hopefully a precursor to clinical studies and FINALLY allowing people with diabetes and the medical profession to know and understand the opportunity that Afrezza offers.... because what has happened so far is pure BS in my opinion. |
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