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Keep in mind that there are at least two products here, NicVax and Ta Nic. The below article is about Ta Nic but both products seem to be working with the "higher dose" now. If true and producing just 16% smoking cessation at one year, that's 5 points less than varenicline (Chantix & Champix) at 21%.But if interested in making semi-valid comparisons among products that have never actually gone head to head, it's critical to keep an eye on a few additional factors: (1) participant expectations going into the study: what did the informed consent process and risk explanations prior to randomization or study recruiting prepare smokers to expect? (2) the ease or difficulty of determining group assignment: could you tell that some amout of smoked nicotine was not arriving in the brain, was the expected dopamine "aaah" sensation significantly smaller than normal, or if in the placebo group were your "aaahs" the same as before and you simply kept smoking and never quit; and (3) education, counseling, study contacts (brief quitter pep rallies) and group support, each having their own effectiveness, independent of the products being evaluated. How much study contact was there, when was it received, and at the time received, what percentage of each group was still present and fully participating in the study; if one group was then substantially larger than the other, did these independent cessation factors influence that group's overall success rate to a greater degree?The 26 provider counseling and/or support contacts in Pfizer's varenicline studies were very likely a record, the most ever in any quit smoking clinical trial. But I get the feeling that Ta Nic and Nic Vax were trying to stand more on their own with vastly less user contact. Still, as to blinding and expectations both the vaccines and varenicline present rather interesting issues.In NRT trials, most of the active group (those receiving replacement nicotine) could sense some level of easing off of the underlying current of withdrawal anxieties which was most stable with the patch but more noticible with oral and nasal nicotine, which was often administered in reaction to urges and craves. The more times the smoker had previously tried to quit and experienced the onset of full blown withdrawal the more they would have come to recognize their withdrawal syndrome.Varenicline is closer to the effects of nicotine, sitting upon and blocking the exact same acetylcholine receptors nicotine would have occupied, while causing 35 to 60% of the dopamine flow nicotine would have generated. After day 5 of using varenicline, when it gets up to therapeutic levels, some user emails to me have described smoking a cigarette as if smoking a carrot - it does absolutely nothing for you, as you don't get the normal and expected "aaah" sensation."This is why any suggestion that varenicline trials were "blind" and users could not correctly guess their group assignment is likely the biggest hoax smoking cessation has "yet" seen. The pharmaceutical industry was allowed to get away with NRT studies not being blind and appears to have become embolden by it.What Pfizer is not telling users is that some day soon they'll stop taking varenicline, the dopamine flow it generates will end, and that in clinical trials half who succeeded in using it for 12 weeks thereafter relapsed to smoking.But turning to blinding in Nic Vax and Ta Nic trials, the active vaccine group had a bit different experience than with NRT or varenicline. Instead of a somewhat diminished withdrawal syndrome or having up to 60% of the dopamine flow that nicotine provided (and 24 hours a day), in theory, vaccine users experience full-blown nicotine withdrawal, as if a member of the placebo group in an NRT or varenicline study, but with one big difference, what would normally have been relapse via smoking nicotine did not cause a dopamine "aaah" explosion in the brain 10 seconds later. How could an event such as this go unnoticed by any nicotine addict? It doesn't.As with varenicline I can't see how vaccine researchers can, with a straight face, proclaim these studies blind. As with varenicline, it is not a matter of "guessing" your study group assignment but actual knowledge that a foreign chemical is present in your body and that your normal smoking experience has been seriously altered.As for placebo group blinding, it too is somewhat unique in that some degree of motivation to quit smoking was to flow from cigarettes not providing their normal effect - relief from the onset of early withdrawal. Again, it's hard to believe that most placebo group members wouldn't have known their assignment.But knowing group assignment is not the end of the analysis as to whether or not the study's results are valid. The question becomes, did assignment awareness combine with expectations to influence the participant's actions? In other words, if you volunteered for a study after learning it involved testing of a new "medication" and that you could get a free 12 week supply of the "medication," how would you react to actual knowledge that you were in fact getting it, or that you were not getting it?If assigned to the placebo group and either still smoking or enduring full blown nicotine withdrawal, would you have stuck around for 12 weeks, 6 months or a year and allowed researchers to toy with you? In the active group, if your expectations had been met and you could actually feel the medication producing a totally new or somewhat different cessation experience, would such knowledge have given you new hopes, extra resolve and had you staying around longer than you otherwise would have, to try even harder and actually return for the study's next scheduled visit?My reason for writing the above is to try and aid you in seeing that things are not always as represented, that should you feel your resolve weakening, that all these news articles and advertisements about new magic cures will hopefully not play even a minor role in inviting relapse. For what we do know is that in all real world quitting method surveys these products have yet to perform better than uneducated and unsupported "one your own" quitting.We've each now arrested our dependency and there is absolutely no guarantee that any of us could ever come this far and heal this much again. There's only one way to stay on this side of the bars while keeping our now arrested dependency on the other ... no nicotine today, Never Take Another Puff, Dip or Chew!John (Gold x8)
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April 30, 2008
An anti-nicotine vaccine will be tested on 400 people in the Nordic countries over the next year aimed at helping smokers kick the habit, the Karolinska Institute in Sweden said on Monday.
"A Swedish vaccine against nicotine will be tested on 400 people in three Nordic countries," the institute said in a statement.
Lena Wikingsson, head of Independent Pharmaceutica, which is running the experiment, told Swedish daily Svenska Dagbladet that people taking part in the study -- heavy smokers who would like to quit -- would be given counselling before they stop smoking and would be given a drug to help them quit.
They will then receive one injection a month for four months. Half of the participants will be given the vaccine and the other half a placebo.
They will be followed for a year to see whether they begin to smoke again, Wikingsson said.
The vaccine, called Niccine, has been developed over the course of 10 years by Swedish researchers at the Karolinska Institute, under the guidance of professor Torgny Svensson who founded Independent Pharmaceutica.
Niccine is supposed to help the immune system build antibodies against nicotine.
If a person who has taken the vaccine smokes a cigarette, the antibodies jump into action, latching onto the incoming nicotine and preventing it from reaching the reward system in the brain -- thereby stopping the smoker from getting the "kick" that makes smoking addictive.
One problem in developing nicotine vaccines is that the immune system doesn't react to normal nicotine.
In order to activate the immune system, the nicotine in the vaccine needs to be latched onto a "carrier" or "host" that stimulates the immune system to create as many antibodies as possible.
For the vaccine to be successful, a large number of antibodies must be created, and the carrier component is therefore the key part of Niccine, Wikingsson said.
"There are several possible applications if the vaccine proves to be effective," Wikingsson told Svenska Dagbladet.
"Nicotine conjugate vaccines stimulate the immune system to develop nicotine-specific antibodies (Abs) using an immunogen comprised of nicotine covalently linked to a larger carrier protein. Conceptually, the mechanism of action is antinicotine Abs binding to nicotine molecules, and the resulting complex is too large to cross the blood–brain barrier. With increasing Ab levels, more nicotine is captured and sequestered in the blood and prevented from entering the brain, leading to a lowering of the reinforcing effects of nicotine. "
Yes, you are reading that correctly. Placebo group six month (26 week) quit smoking rates were actually higher than among the 70% of quitters whose immune systems generated the lowest antibody response, generating a 12% six-month placebo quitting rate versus only 9.3% for those receiving NicVax. Placebo won again at one year with a 10% quit smoking rate versus only 7.1% among 70% of NicVax quitters receiving 4 or 5 injections.High-Ab responders to 3′AmNicrEPA were defined as the top 30% of responders by area under the curve (AUC) (0–26 weeks) and the low-Ab group as the bottom 70% of responders. 3′AmNic-rEPA recipients in the high-Ab group were significantly more likely to attain 8 weeks of continuous abstinence from smoking from weeks 19 through 26 than were those receiving placebo (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14–6.37). No significant differences in results were observed between the 3′AmNic-rEPA low-Ab group and the placebo group (9.3% vs. 12.0%, P = 0.46). As a secondary outcome, continuous abstinence rates (CAR) to 52 weeks were evaluated from weeks 19–52; these were significantly higher in the high-Ab group relative to the placebo group (19.7% vs. 10.0%, P = 0.044, OR = 2.64, 95% CI 1.03–6.79); in contrast, there was no significant difference in results between the low-Ab group and the placebo group (7.1% vs. 10.0%, P = 0.43).
Hatsukami DK, Jorenby DE, Gonzales D, Rigotti NA, Glover ED, Oncken CA, Tashkin DP, Reus VI, Akhavain RC, Fahim RE, Kessler PD, Niknian M, Kalnik MW, Rennard SI.
Conflict of Interest
R.C.A., R.E.F.F., P.D.K., M.W.K., and M.N. are employees of Nabi Biopharmaceuticals and have received salary support, stock, and stock options. All other authors were investigators on the clinical trial funded by NIDA and by Nabi Biopharmaceuticals, and some served on an advisory panel. D.E.J. has received research support from Pfizer. D.G. owns shares of Pfizer and has received grant/research support from Pfizer, Addex Pharmaceuticals, Sanofi-Aventis, and GlaxoSmithKline; consulting fees and honoraria from Pfizer, GlaxoSmithKline, and Evotech NeuroSciences; and speaker fees from Pfizer. N.A.R. has received research grant support from Pfizer and is an unpaid consultant to Pfizer and Free & Clear. E.D.G. has received grants from and served as a speaker and consultant for Pfizer. He has also provided advice to or is on the advisory board/panel of Pfizer. He has also served as a speaker for Nabi Biopharmaceuticals. C.A.O. has received grant funding from Pfizer. S.I.R. has participated as a speaker in scientific meetings and courses under the sponsorship of AstraZeneca, GlaxoSmithKline, and Pfizer; has served as consultant for several pharmaceutical companies with relevance to the topics noted in this study (Almiral, Altana, Amersham, Array Biopharma, AstraZeneca, Aventis, Boehringer Ingelheim, Critical Therapeutics, GlaxoSmithKline, Globomax, Intermune, Merck, Novartis, Ono, Otsuka, Roche, Sanofi, Scios, Wyeth); serves on advisory boards of Altana and Pfizer; has been sponsored by GlaxoSmithKline to conduct several clinical trials and received laboratory support; has conducted clinical trials sponsored by Roche, Pfizer, Sanofi, and Novartis; has conducted both clinical trials and basic studies under the sponsorship of Centocor; and has conducted basic studies under the sponsorship of AstraZeneca. This paper was presented in part at the American Heart Association Scientific Sessions 2007, Orlando, FL, 7 November 2007