The results will show in the most convincing way why DBS will be one of the next therapies for dementia and have serious implications for the future treatment of patients with the disease.
Surgical treatment of Alzheimer’s disease is the subject of a series of posts in this blog series. Most of the results of these studies are in the literature; many of them can be found in references I will quote at the end of the post. On Tuesday, February 8th, the first phase 4 phase 3 randomized clinical trial of high intensity repetitive transcranial magnetic stimulation (rTMS) for initial clinical trials for early onset Alzheimer’s disease was proposed by the French researchers. The results of this initial phase 3 clinical trial are awaited now, as the trial will not be complete until March 2017.
The key difference between the two clinical trials is that the former will use an extremely sensitive technique in a noninvasive way for the therapy (rTMS), while the latter will use a different method for the therapy (high intensity repetitive transcranial magnetic stimulation). The study will probably follow a well-defined protocol, taking into account the difference of these two therapy techniques. There is good reason for why rTMS is used. It has a low rate of side effects compared to current, conventional treatments. The procedure is very safe for both patients and researchers, so no safety warning is given that is expected for conventional treatments.
More details about the French study can be found here . I must warn that the details are very sensitive, as well as very long and detailed. Some of the more obvious things that you would want to know are that the dose of rTMS is extremely low (around 5 mcgmin/kg), and that a very precise timing is needed. For other details, you can read my blog posts about the details of these trials. The first phase 4 clinical trial using rTMS for the treatment of early-onset Alzheimer’s disease (AAD) has been proposed by the Spanish neurologist, Alejandro J. Barreto who first proposed the idea during his doctorate at the University of Madrid in 2015.
The main purpose of this study is to evaluate the effect of different treatment regimens in order to optimize the effect of the treatment. The treatment regimen of the study will be different from the previous ones in order to optimize the treatment, so if the results are positive, we can expect a second phase of the trial to include even more patients. In this second phase, the protocol is not yet final. The second phase will be submitted to the Spanish Clinical Trials Office next week.
So there is still a very long way to go until at least clinical trials. But let’s have a look at the data from the Spanish phase 4 trial . This study is not a large, but a recent study, and a good study. The trial is scheduled to start in April 2017. After a very strict set of safety procedures, the study is also a double-blind trial, though of course it depends on whether the trials will be double-blind.
Among the main findings of this study are the following:
The primary endpoint is a reduction in the severity of cognitive decline after 4 (and 6) months of treatment. The major weakness of the study was that most patients are receiving a second treatment for one of the drugs (as with many other medical studies with long follow up in the past) and patients receive two different treatment regimens. This is an issue that concerns all of the most high-profile clinical trials, and it’s also known as an ‘asymmetric’ study, where both patients receive two different treatments. It may not be uncommon to see outcomes that do not follow standard clinical protocols, but in this case the main outcome was a reduction in the cognitive decline as compared to the baseline. The main difference between this study and the other studies of the past, where patients receive treatment for an average of four years, may be because the Spanish study was designed to assess the effects of the treatment within each month, whereas the other trials monitored the effects over the longer term in order to eliminate the problem of long follow-up.
According to the results of this study, the two treatment groups showed equal performance on a series of cognitive tests at week one, although they achieved worse scores on the test given after six and 11 months. By week 12, however, it’s a clear improvement of the treatment for both groups. It is hard to judge the effect of the treatment on the first 12 months (particularly the scores in the testing on day 18 of follow up), but again, the main result is in the last phase of the trial:
The main outcome of the trial was a reduction in the time in which the average score on a cognitive test, which was then followed up for up to 52 months, decreased;