2012 European SRNT Conference highlights e-cigarette studies and treatment for Parkinsons

[Vocalek]

The European Society for Research on Nicotine and tobacco publishes abstracts of the presentations. The book of abstracts can be downloaded here: http://www.srnteurope.org/assets/Abstract-Book-Final.pdf

Here are some interesting abstracts:

Page 16

W1 E-CIGARETTES: CURRENT STATUS AND FUTURE CHALLENGES
W1-1 E-CIGARETTES: THE VIEWS OF SMOKING CESSATION STAFF IN THE UNITED KINGDOM
W1-2 ELECTRONIC CIGARETTES FOR SMOKING CESSATION: A RANDOMISED CONTROLLED TRIAL

Page 17

W1-3 USE OF ELECTRONIC CIGARETTES AMONG POLISH ADOLESCENTS AND YOUNG ADULTS
W2 ROLE FOR NICOTINE AND nAChR-TARGETED THERAPIES FOR PARKINSON’S DISEASE
W2-1 SUBUNIT COMPOSITION, PHYSIOLOGICAL ROLE AND REGULATION OF NATIVE nAChR SUBTYPES IN THE MESOSTRIATAL DOPAMINERGIC PATHWAY

Page 18

W2-1 NOVEL APPROACHES TO STUDYING ALPHA6BETA2* NICOTINIC RECEPTORS [Note: This is mislabeled. Should be "W2-2"]
W2-3 THE NIGRO-STRIATAL PATHWAY NICOTINIC RECEPTOR SYSTEM: ADAPTATION, ACTIVATION AND DESENSITIZATION

Page 19

W2-4 POTENTIAL FOR NICOTINE AND NICOTINIC RECEPTOR DRUGS FOR PARKINSON’S DISEASE THERAPEUTICS – EVIDENCE FROM ANIMAL STUDIES
W2-5 Nicotinic Modulation of Cognitive Function: Therapeutic Implications for Parkinson’s Disease
W2-6 NICOTINIC ACETYLCHOLINE RECEPTORS IN DRUG DEVELOPMENT FOR NEURODEGENERATIVE AND COGNITIVE DISEASES

I have to admit that the W2-1 through W2-3 were well over my head. But I found it fascinating that they are finally taking a good hard look at using nicotine (and related chemicals) as treatment for Parkinson's. This strikes close to home, as I watched my mother slowly losing her mobility and her sanity to Lewy Body Disease, a form of dementia caused by the same proteins (Lewy Bodies) that cause Parkinson's.

This is from W2-4:

Relevant data from diverse clinical populations including PD, mild cognitive impairment, and attention deficit hyperactivity
disorder will be presented to illustrate a potential role of nAChR receptors in cognitive deficits and difficulty with behavioral control in PD.

 

[Vocalek]

And this one deserves an entry of its very own:

P54
THE EFFICACY AND SAFETY OF AN ELECTRONIC CIGARETTE (ECLAT) STUDY: A PROSPECTIVE 12-MONTH RANDOMIZED CONTROL DESIGN
STUDY
Pasquale CAPONNETTO1,2, Davide CAMPAGNA1,2, Fabio CIBELLA3, Jaymin B. MORJARIA4, Cristina RUSSO1,2, Riccardo POLOSA1,2
1 Centro per la Prevenzione e Cura del Tabagismo
(CPCT), Università di Catania, Catania, Italy
2 Institute of Internal Medicine, Università di Catania,
Catania, Italy
3 Instituto di Biomedicina e Immunologia Molecolare del
Consiglio Nazionale delle Ricerche, Palermo, Italy.
4 School of Medicine, University of Southampton,
Southampton General Hospital, UK

Background: Recent evidence suggests that E-cigarettes may be an effective and safe aid to smoking cessation, and large randomized controlled trials are now required to confirm and expand these preliminary observations. We designed a double-blind, placebo-controlled, randomized clinical study to evaluate smoking reduction, smoking abstinence and adverse events in smokers not intending to quit experimenting two different nicotine strengths of a very popular E-cigarette brand (‘Categoria’; Italy). Methods: A double-blind, sham-controlled, randomized, clinical trial of 300 smokers (unwilling to quit) was designed to assess the efficacy and safety of ‘Categoria’ E-cigarette (Arbi Group, Italy) loaded with 7.2 mg nicotine (study group A) and 4.8 mg nicotine (study group B) cartridges in comparison to no-nicotine containing cartridges (study group C). Study participants were invited to attend a total of nine study visits in 1-yr during which product use, number of cigarettes smoked, and exhaled carbon monoxide (eCO) levels were recorded. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed. Analyses were computed as per intention-to-treat. Results: A significant reduction in mean cig/day use and eCO levels from baseline was recorded at all study visits in all three study groups. A mean of 2.0 cartridges/day was used in each study group up to the 3-month time point, but falling thereafter. 50% reduction in the number of cig/day was shown in 21% and 9% participants in group A, in 16% and 8% in group B and in 19% and 10% in group C, at month-3 and -12 respectively. Smoking abstinence was observed in 11 % and 13% participants in group A, in 17% and 9% in group B and in 4% and 4% in group C, at month-3 and -12 respectively. Only minor and transient adverse events were reported, including mouth and throat irritation, and dry cough. By and large, participants’ perception and acceptance of the product was positive.
Conclusion: In smokers not intending to quit, the use of e-Cigarette decreased cigarette consumption and elicited enduring tobacco abstinence at 1-yr without causing significant side effects.

Funding: None of the authors have any competing interests to declare, with the exception of RP. RICCARDO POLOSA has received lecture fees from Pfizer and GSK, a research grant from Pfizer, and he served as a consultant for Pfizer, Global Health Alliance for treatment of tobacco dependence, and Arbi Group Srl.

NOTE: The e-cigarette brand used in this study labels the nicotine content based on the total milligrams of nicotine in the cartridge. Therefore, those using two cartridges in Study Group A were getting a daily dose of 14.4 mg. Those in Group B were getting 9.6 mg, and those in Group C were getting 0 mg. The cartridges, I am told, hold about 1/3 ml.

I find it interesting that abstinence went up from 11% to 13% in Group A between the 3-month and the 12-month mark. It went down in Group B (from 17% to 9%,) and stayed the same in Group C.

 

[rolygate]

This trial seems to show that, at the 12 month mark, 13% in group A (those receiving the 'highest' nicotine dose) had completely switched to an ecig or quit totally. It is a fairly low number, but against that it may be the case that these smokers did not intend to quit and were offered what appears to be ultra low performance obsolete equipment and then additionally restricted.

If indeed they did not want to quit, then 13% is an impressive figure as it equals or exceeds the best possible result for the best-performing pharmacotherapy, Chantix, under ideal conditions: smokers who want to quit, who are mentored throughout the trial, and for whom the pharmaceutical both works and does not need to be ceased due to the side effects. It might also be noted that a similar group of 100 Chantix-receiving patients would experience three heart attacks (1 in 30 Chantix recipients experience a cardiac event, as demonstrated by several independent clinical studies).

A 13% success rate at 12 months is also about double the best result for NRTs given to strongly-motivated quitters, so even these obsolete, low-performance ecigs with very low nicotine dosage are shown to be not just twice as effective as NRTs (typical result = 7% success at 12 months in motivated quitters), but since the subjects were unmotivated to quit, an unknown amount superior.

The mentoring support given would also be nice to know. 13% is frankly an incredible figure when the equipment is considered - obsolete models seem to have been supplied, with ultra-low performance together with low nicotine dose and a tightly-limited daily supply far below the average cigarette number equivalence.

The reasoning behind this is:

1. If the refill container is described as a cartridge and holds 0.3ml then it cannot be a cartomiser, the smallest of which holds about 1ml (~22 drops). A regular 510 cartridge holds about 0.6ml or ~12 drops, so this is also excluded. Cartridges that hold 0.3 ml are used for the old 206 and M401 systems and similar devices. These have a protruding atomiser (not recessed like the 510) and a small cartridge that fits over the atomiser. These 'super-minis' were popular about 4 years ago and were overtaken by the 510 and KR808 minis, which performed better. These were then themselves overtaken by the mid-size models like the eGo.

The performance of a super-mini is best described as 'extremely sub-par' in today's terms, since all current measurements should be performed with a mid-size model such as the eGo, as this is the current benchmark. 92% of non-naive users polled upgrade to an eGo or larger model.

2. If a cartridge contains 0.3ml and has a total of 7.2mg of nicotine (for group A in the trial), then one ml would be of 21.6mg strength: 7.2 x 3 = 21.6

As this strength does not exist commercially, perhaps the 0.3ml figure is inaccurate, and we could take the nearest retail strength as being more likely: 18mg.

If a cartridge contains 0.3ml and has a total of 4.8mg of nicotine (for group B), then one ml would be of 14.4mg strength: 4.8 x 3 = 14.4

As this strength does not exist commercially, perhaps the 0.3ml figure is inaccurate, and we could take the nearest retail strength as being more likely: 12mg

A cartridge with 0.3ml is probably equivalent to about 2 to 3 cigarettes. The generally-accepted equivalency is 3 to 4 drops per cigarette, and 1ml or ~22 drops is about 5 or 6 cigarettes. Two cartridges per day, as allowed, are equivalent to about 5 cigarettes.


So what we are looking at is ultra low-performance equipment loaded with low-strength nicotine and with use restricted to a fraction of the daily cigarette intake. Multiple clinical trials have shown that this combination delivers zero or very little nicotine to the user (blood plasma nicotine tests showed zero increase or tiny amounts present after use [Vansickel & Eissenberg 2010 aka 'Eissenberg 1'; Bullen et al] ).

Intellicig's clinical trials (unpublished) also showed this, which led to them introducing the 45mg strength that they now sell for use with low-performance equipment, and for which they are likely to receive a medical license soon.

Only equipment capable of delivering a proven blood plasma level of 15ng/ml or higher should be used, otherwise you are essentially looking at a placebo.

The supply of two cartridges per day of 2 or 3 cigarettes' equivalent is also sub-optimal for success, and it is hard to work out why a trial would limit this factor when NRT trials do not do so.

All things taken together, any success at all in this trial must be seen as remarkable since as far as most of the subjects wourld be concerned they were supplied with a placebo. It would be possible to multiply the success rate by a factor of three or four, even for unmotivated quitters, by optimally managing the trial:

- Supply equipment that works according to current standards, such as an eGo / Riva / Kgo etc. The supply of obsolete equipment may represent certain market situations but is not optimal if potential success is being researched.

- Supply 45mg liquid strength or less, according to individual requirements (people have a factor-10 difference in tolerance to nicotine and supply must be tailored to the individual). If you do not supply 45mg nicotine for those who need it with low-performance equipment, then you are simply providing a placebo (as demonstrated by several clinical trials).

- Supply the equivalent of 20 cigarettes a day or whatever the individual requires; obviously, supplying a 5-cigarette equivalent to a 60-a-day smoker is not going to have high success rates.

- Supply a choice of head systems according to preference: one of the most important things to emerge from experience of ecig users is that they have widely-differing preferences for the delivery system, which is now totally flexible and has little relation to obsolete equipment such as the old atomiser-cartridge arrangements.


These trials are interesting, but it is hard to work out what is being tested. If you want to see what potential the system has you wouldn't do it anything like this; it's like claiming you are testing how fast a runner can do 100 metres, but putting a 100-pound load on their back and one foot wearing a stiletto heel shoe. If you did it 'normally' they can do it three times faster. If you ran a trial like this properly you'd get a three times higher success rate if not more, since 'normal', now, is far removed from the conditions in this trial. It represents people limited to very old equipment; limited to a system that is demonstrated to to supply zero nicotine or very little; and limited to 5 cigarettes a day when they might have smoked 40 or more.

If I wanted to get a friend or family member to switch to an ecig successfully I wouldn't do it anything like the process used in this trial, it would be guaranteed to fail. In fact the most interesting feature is how they got anyone to succeed, it's unexplainable and even remarkable.

 

[cyberwolf]

"Conclusion: In smokers not intending to quit, the use of e-Cigarette decreased cigarette consumption and elicited enduring tobacco abstinence at 1-yr without causing significant side effects." Given the fact that participants were given a relatively low nicotine level and sub-par electronic cigarettes, this is indeed impressive. It lends scientific evidence to what many of us have already experienced - that it is possible to quit tobacco with an ecig, even if you don't intend to.

 

[rolygate]

A 13% 12-month success rate under these conditions is remarkable.

I'd guess that there is a 1 in 20 chance of success using the system outlined, so perhaps some of the participants did what any sensible person would: searched the web for a better solution when they realised the concept was valid but the equipment wasn't much use, and used that as well as or instead of what the clinicians were providing. Then returned the original gear when the 12 months was up.

Not sure how many new batteries and heads it would take to get through a year's exclusive use, but I'll bet the figures don't tally with what experience shows is required - several batteries, several atties, and a bunch of carts

Not trying to knock it, but it's hard to understand how the figures are so good.

 

[TennDave]

I agree with sub-par equipment and not enough nicotine.
I have neighbors that are still smoking.
Oh, yeah, they tried e-cigs- wasn't any good for them- too expensive and couldn't keep any vapor going.
They've tried it and it didn't work. I show them my set-up and they shake their head...they've been there and are turned off to it now.
If only I was vaping when they tried to quit w/ ecigs. I would have started them with the good stuff from the get-go.

 

[rothenbj]

Having started with the original Blu kit and quickly moved to 510 manuals you got a tremendous improvement. That being said and keeping ancient history short, the quality stuff available today at a cost in the range of the original Blu kit is quite amazing.

The issue I see is getting people from the cigarette to this advance equipment. A smoker generally wants to duplicate their smoking experience when looking at an e cig- tobacco flavors in a device that has the look and feel of a cigarette. If they can quickly make that jump to the better equipment and the vast array of flavors, they can quickly realize that "smoking" can be much more enjoyable vaping non-conventional kits.

 

[Vocalek]

This is interesting. It has photos of some of the presenters.

http://escapetheanalog.blogspot.com.es/2012/09/hooray-for-helsinki-new-ecig-studies.html?m=1

 

[Spazmelda]

Way down at the end was also this presentation of some of the Clearstream data:

RRP17
CYTOTOXICITY OF ELECTRONIC CIGARETTE VAPOR EXTRACT ON CULTURED MAMMALIAN FIBROBLASTS (CLEARSTREAM-LIFE PROJECT): COMPARISON WITH TOBACCO SMOKE EXTRACT Giorgio ROMAGNA1, Elena ALLIFRANCHINI1,
Elena BOCCHIETO1, Stefano TODESHI1,
Mara ESPOSITO1, Konstantinos FARSALINOS2

1 Abich biological and chemical toxicology research laboratory, Verbania, Italy
2 Onassis Cardiac Surgery Center, Athens, Greece

Background: Electronic cigarettes (e-CIG) have been introduced to the market in recent years as a smoking alternative. We have designed a set of research proto- cols to evaluate the safety of e-CIG on human health (ClearStream). The cytotoxic effects of e-CIG vapor have not been studied. The purpose of this study was to evalu- ate the in vitro cytotoxic effects of e-CIG vapor extract on cultured cells and to compare them with the cytotoxic- ity of regular cigarette smoke extract (ClearStream-LIFE). Methods: We performed MTT-assays on cultured murine fibroblasts (3T3) according to UNI EN ISO 10993-5 stand- ard. We tested 10 different commercially available e-CIG liquids (FlavourArt, Italy) with nicotine concentration of 9mg/ml and a commercially available cigarette (contain- ing 1mg nicotine, 10mg tar and 10mg carbon monox- ide). Standardized smoking machine conditions (35-ml puff volume, 60-s puff interval and 2-s puff duration) were used. The extracts were transferred in a 96-well micro- titer plate in 1:1 to 1:32 dilutions. After 24 hours incuba- tion, viability was measured spectrophotometrically. Both percent viability and inhibitory concentration 50 (IC50) were measured, with reduction of cell viability of more than 30% considered as cytotoxic effect. Results: Regu- lar cigarette smoke extract showed significant cytotoxic effects at dilutions less than 1:8 (viability: 72.8 ± 9.7% at1:8,5.9±1.9%at1:4,9.4±5.3%at1:2and5.7± 0.7% at undiluted extract). The IC50 of cigarette smoke extract was 0.16ml/ml. For e-CIG liquids extract, viability rate was: 98.8 ± 6.9% at 1:32 (P = 0.043), 98.6 ± 7.6% at 1:16 (P = 0.001), 98 ± 7.1% at 1:8 (P < 0.001), 96.2 ± 5.4% at 1:4 (P < 0.001), 94.2 ± 5.7% at 1:2 (P < 0.001) and 89.9 ± 8.9% at 1:1 (P < 0.001). The IC50 of e-CIG vapor extract could not be measured since survival was higher than 50% at all dilutions. Conclusion: Although smoke extract exhibited significant cytotoxic effects, no cytotoxicity was observed from e-CIG vapor extract on cultured mammalian fibroblasts. Electronic cigarette may be a safer alternative to regular cigarette smoking. Funding: The research was funded by FlavourArt, Italy.

 

[rothenbj]

Way down at the end was also this presentation of some of the Clearstream data:/QUOTE]

Utah Vapers - Clearstream Air Results

 

[Spazmelda]

Way down at the end was also this presentation of some of the Clearstream data:/QUOTE]

Utah Vapers - Clearstream Air Results

I think this was a different one? This one seems to be about cytotoxicity in cell culture rather than compound produced from passive vaping. I think I've seen it before, but I was pointing out that it was in the presentation book.

 

[Vocalek]

Was this in the presentation book?

http://clearstream.flavourart.it/site/wp-content/uploads/2012/09/CSA_Poster.pdf