An important article appeared in JAMA today
http://www.physorg.com/news132334654.html
which, while not providing a dramatic cure for dementia, surely gives us the double-blind, placebo comparison that shows that melatonin in combination with supplementation of bright lighting can significantly slow the progress of dementia.
Would that all researchers could see that the design of such an experiment is easy and the results much more acceptable to the scientific community. Just pause, think, set up some controls and run the experiment. And don't publish the anecdotal results that led you to the hypothesis that your are testing in the double-blind experiment. Now was that so hard?

Hi Bill,

This is indeed good news, and I will keep telling my Dad who likes to leave lights off, to turn them on for Mom!

On the other hand, I know that you are implying that studies should all be done this way, and perhaps you are right, but it doesn't mean that other studies are false because they didn't use placebos, or haven't gotten that far yet. I could never be a doctor who had to give someone a placebo for 6 months, knowing and watching them suffer and decline when I had something available to help them now!

A new study just came out today regarding Etanercept (the same drug that my Mom is getting Perispinally for Alzheimer's)for back pain by a group in Japan. It was a Double-Blind Clinical Trial, and it proved what Dr. Tobinick told the medical profession in a preliminary study he did years ago -- Not double-blind - but a proven clue showing studies should be done. This is the first study: http://www3.interscience.wiley.com/journal/119818101/abstract
Title:Exogenous tumor necrosis factor- rapidly alters synaptic and sensory
transmission in the adult rat spinal cord dorsal horn

Conclusion of the Human Study (I have a PDF File I will put up separately, was hoping to find a link): The results of this randomized study support that caudal
epidural injection of ETN for lumbar ridiculer pain in patients with disc
herniation-induced sciatica is efficacy and safety, is potential to be quick
recovery from the pain.

This is a quote from Dr. Tobinick's Study, hypothesising exactly what this new study proved, the title of their study says what he said years ago, and he treated over 3000 patients successfully. He has made the same statements regarding Perispinal Etanercept for Alzheimer's:
"Synaptic dysfunction has gained increasing recognition as an important pathophysiological component of Alzheimer's disease [28-32]. Recent evidence suggests that TNF-alpha may be involved in this synaptic dysfunction [33-37]. Although TNF-alpha is most widely known as a pro-inflammatory cytokine, basic science studies suggest that TNF-alpha may also have entirely different functions in the Alzheimer brain: as a regulator of synaptic transmission....The authors hypothesize that excess TNF-alpha in Alzheimer's disease[5,7-10,12,14,16,18,23] interferes with the synaptic regulatory functions of TNF-alpha. When TNF-alpha is in a normal physiologic range synaptic scaling is enabled, thereby preserving optimal functioning of the brain's neural network. When TNF-alpha is overexpressed, due to glial activation, it is postulated that the synaptic regulatory activities of TNF-alpha are disturbed. Synaptic dysfunction is hypothesized to result from this dysregulation, which may provide a basis for reduced functional connectivity between brain regions in Alzheimer's disease [57,58]. The rapid effects of perispinal etanercept are hypothesized to be the result of rapid neutralization of excess TNF-alpha, which thereby ameliorates this synaptic dysregulation, allowing normal cross talk between different regions of the brain."

Dr. Tobinick gave researchers/pharma companies the clue, they are the ones who should have done the Double-Blind placebo study, same as the Perispinal Etanercept (Enbrel) study for Alzheimer's. Clinical Trials cost Hundreds of millions of dollars. How many Private Practice Doctors do you know that have that kind of money?

I for one am happy that he kept treating patients even though a double-blind clinical trial hasn't been done yet. He's been waiting for years for someone to do it. I finally became aware of it, and my Mom improved, and is now maintaining because of it.

Studies done right are important, but they have to start somewhere...it's just that sometimes the "Boy really saw a Wolf", but the village didn't believe him!

I know this study isn't regarding AD, but it is regarding the effectiveness of the drug ETANERCEPT, which is a TNF inhibitor that has been shown to help AD patients like my Mom:

OP-0261 THE EFFICACY AND SAFETY OF CAUDAL EPIDURAL INJECTION WITH THE TNF-ALPHA ANTAGONIST, ETANERCEPT, IN PATIENTS WITH DISC-HERNIATION-INDUCED SCIATICA. RESULTS
OF A RANDOMIZED, CONTROLLED , 1-MONTH FOLLOW-UP STUDY.
k. kume*1, k. amano1, k. amano1, s. yamada1
1rheumatology, Hiroshima Clinic, hiroshima, Japan
Background: TNF-alpha is among the chemical factors involved in diskrelated sciatica.
Objectives: To determine the efficacy and safety of caudal epidural TNF
blockade with etanercept (ETN), in patients with disk-herniated sciatica.
Methods: Inclusion criteria were unilateral acute severe sciatic pain with an MRI-confirmed disc herniation concordant with the symptoms and signs of radicular pain. All patients had to be candidates for discectomy, as evaluated by two independent orthopedic surgeons. Twenty-eight patients were allocated to a single caudal epidural injection guided by fluoroscopy
of either 25 mg etanercept (ETN) or placebo.
Assessments at baseline and various time points( every day after injection) included clinical examination with straight leg raising restriction(SLR), questionnaires related to subjective symptoms(leg and back pain by 100-
mm visual analog scale,VAS), number of discectomies ,and adverse events possibly related to treatment. The primary endpoint was a reduction in leg pain from baseline to 1 week, which was analyzed using a Mann-
Whitney U test and repeated-measures analysis.
Results: At 1 day, a significant reduction in pain was observed in both groups. And pain on the VAS for ETN was a significant decrease than
placebo. Pain on the VAS for ETN was baseline mean 80.3(SD 19.6)mm, 1day after injection 45.6(25.1)mm(p<0.001), placebo baseline 78.0(SD
18.5)mm, 1 day after injection 58.2(SD 21.9)mm(p=0.34). At 1 month, a significant reduction in pain was observed in both groups,
with no significant difference between treatment regimens. Pain on the VAS for ETN was 1 month after injection mean 32.6(22.5)mm, placebo 1 month after injection 33.4(SD22.1)mm. Similar efficacy was observed between treatment groups at 1 month after injection. Eleven patients in each group required surgery. No adverse events(shock, allergy, infusion
reaction and etc.)were encountered within 1 month. At 1 day, a significant reduction in pain was observed in both groups. And
pain on the VAS for ETN was a significant decrease than placebo. Pain on the VAS for ETN was baseline mean 80.3(SD 19.6)mm, 1day after
injection 45.6(25.1)mm(p<0.001), placebo baseline 78.0(SD 18.5)mm, 1 day after injection 58.2(SD 21.9)mm(p=0.34). At 1 month, a significant reduction in pain was observed in both groups, with no significant difference between treatment regimens. Pain on the
VAS for ETN was 1 month after injection mean 32.6(22.5)mm, placebo 1 month after injection 33.4(SD22.1)mm. Similar efficacy was observed
between treatment groups at 1 month after injection. Five patients in ETN and 4 patients in placebo required surgery respectively. No adverse effects related to treatment (shock, allergy, infusion reaction, infection and etc.)
were encountered within 1 month.

Conclusion: The results of this randomized study support that caudal epidural injection of ETN for lumbar ridiculer pain in patients with disc herniation-induced sciatica is efficacy and safety, is potential to be quick
recovery from the pain.

References: The treatment of disc-herniation-induced sciatica with
infliximab: one-year follow-up results of FIRST 2, a randomized controlled
trial. Spine. 2006 Nov 15; 31(24):2759-66
TNF-alpha and phosphorylation of ERK in DRG and spinal cord: insights
into mechanism of sciatica. Spine. 2006 Mar 1;31(5)523-9

Hi, Felicia,
The Yaun, et al, article,
http://www3.interscience.wiley.com/journal/119818101/abstract
is about spinal cords. Not a word about brains. Therefore it does not say anything about Tobinick's conjecture regarding brain TNF-alpha.
The kume, et al, paper is about sciatica and pain anatomically far below the brain.
These two papers do not seem to have any relationship to Tobinick's work.

Hi Bill,

You're right that it wasn't regarding AD, but what I was stating is that Dr. Tobinick was right about his studies and it has now been proven. Many neurologists don't want to believe he is a true scientist, and these studies should help open their eyes to his treatment for AD. That is what I'm praying for anyway!

What they have in common is the findings regarding TNF inhibitors. Many people have questioned Dr. Tobinick's hypothesis, and now the clinical trials and studies are coming out to prove that he was correct. This all started with his back pain treatment, then he found a correlation with dimentia patients.

In the Japan study, they used etanercept, but injected it through an epidural procedure which is very invasive as compared to Perispinal, which is the method Dr. Tobinick discoivered. The results seemed to be the same with epidural injection as perispinal, so if I was the patient, I would definitely choose perispinal since in is just an injection given in the correct local with no risk to the spine or spinal fluid leakage.

Is there ANY possibility that we could have a post about a properly-configured melatonin study that DOESN'T mention Enbrel? Double-blind studies are extremely important and THANK GOD most legitimate researchers UNDERSTAND this!

The thread was called: An example of very good research, and I put up my opinion of one. It included a double-blind placebo controlled study, regarding a Drug (not the procedure, but the drug) that has been helping AD patients. It's was exciting to me to find these results, which support the work of the man that found the drug to be helpful to AD patients.

Again, as on another thread, you are suggesting that I not to post my opinion when that is what forums like this are all about!

Sorry if it isn't what you agree with, I don't agree with your opinion, but I haven't told you not to post it, so please don't ask me not to post my opinion.

I believe you are trying to do what is right, but so do I. I respect your opinion because I know you have been a caregiver for a long time, and you have so much wonderful experience. I haven't gotten to the point of "acceptance" of letting the disease progress, and if I can help it and if my opinions are right, I never will have to.

Felicia

Felicia, please read the words I say and don't put ones there that I didn't. I have not asked you not to share your opinions - I have requested that the discussion stay on-topic. I think it's important to stay on-topic so that information can be easily found and not all jumbled together with bits and pieces here and there between long posts of stuff that does not have a clear bearing on the discussion at hand.

There is a thread for Enbrel discussion. Not every thread in the treatments forum has to contain references to Enbrel! Deluging other topics with Enbrel is not considerate to folks who might wish to discuss something else as a treatment or proper clinical design structure - that's called hijacking a topic.

Proper testing is essential for responsible treatment and double-blind studies are needed because one has to PROVE efficacy and eliminate the placebo effect. There is no other way to do so other than to test in this manner. While your concern is focused on your mom, the focus of getting new treatments accepted for EVERYONE has to consider MANY aspects of patient care and individuals and it begins with SOLID scientific testing and evidence. While our system is not anything near perfect, doing the testing has to happen before mainstream health care practitioners and insurance companies will accept an experimental drug or procedure. Why the rules of scientific testing and proof should be changed for Enbrel or Dr. T. is not clear to me...

Your pioneering spirit is admirable as is that of ALL the noble people who participate in clinical trials not knowing whether they are getting the placebo or the drug. They do it based on hope for themselves and the sincere desire to help others, even if it doesn't work out for them. They risk not having an overnight success, any success, or even ill effects which could cost them their lives prematurely or cause debilitating conditions they did not have before the therapy. While I share your impatience, I understand WHY the proof and proper testing design is essential and fully support it.

"I haven't gotten to the point of "acceptance" of letting the disease progress, and if I can help it and if my opinions are right, I never will have to."

I hope things work out that way for you, but it isn't the case with everyone. AD is not the ONLY cause of dementia. Some people are very old and have other health issues besides AD. Acceptance is not a bad thing, simply one of the steps along the way when one has exhausted all reasonable avenues of treatment for a terminal illness. Do NOT assume that because some people prefer to scrutinize a treatment more than you do that they are "accepting" anything... to do so insults the integrity, intentions and motivations of others with which you may not be aware or familiar.