Troubles du Spectre Autistique :arrêt des essais de phase 3 évaluant le diurétique bumétanide faute d’efficacité (Coline Carré. Le Quotidien du Médecin)
C’est une déception. Les laboratoires Servier et Neurochlore annoncent ce 7 septembre l’arrêt anticipé de leurs deux essais cliniques de phase 3 lancés en 2018 pour évaluer le diurétique bumétanide (Burinex) dans la réduction des troubles du spectre autistique (TSA). « Aucun signe d’efficacité n’a été observé (…). Les résultats de ces études n’ont pas démontré la supériorité de la bumétanide par rapport au placebo », expliquent-ils dans un communiqué commun.
Les deux études randomisées de phase 3 en double aveugle versus placebo devaient évaluer ce diurétique − déjà commercialisé dans le traitement de l’insuffisance cardiaque et de certains œdèmes − dans 14 pays, dont 11 en Europe, dans le cadre d’un Plan d’investigation pédiatrique accordé par l’Agence européenne du médicament (EMA).
422 enfants inclus, de 2 à 17 ans
Le premier essai incluait 211 enfants de 2 à 6 ans, le second, autant, mais âgés de 7 à 17 ans. Ils ont été suivis 6 mois en double aveugle contre placebo, avant de poursuivre sous bumétanide 6 mois supplémentaires. Les critères principaux d’évaluation portaient sur les symptômes clés des TSA : les altérations de la communication et des interactions sociales en présence de comportements stéréotypés et répétitifs.
« Aucun des critères d’efficacité, principal (CARS – Childhood Autism Rating Scale) comme secondaires (SRS – Social Responsiveness Scale -, CGI Scale – Clinical Global Impression Scale -, Vineland), n’a été atteint après 6 mois de traitement, que ce soit chez les enfants âgés de 2 à 6 ans, ou chez les enfants et adolescents âgés de 7 à 17 ans. Les études n’ont révélé aucun problème de sécurité inattendu associé à l’usage de la bumétanide », lit-on.
Un espoir né en 2012
« Les résultats des études cliniques de phase 3 sont une déception majeure », reconnaît le Pr Yehezkel Ben-Ari, président de Neurochlore, société de biotechnologie qu’il a fondée en 2012, avec l’espoir d’améliorer les enfants atteints de TSA en réduisant, grâce à ce diurétique, la concentration intraneuronale en chlore. Directeur émérite de l’Inserm et fondateur de l’Institut de neurobiologie de la Méditerranée, il venait alors de cosigner avec le Dr Éric Lemonnier, pédopsychiatre au CHRU de Brest, une étude prometteuse, portant sur 60 enfants autistes et Asperger, qui montrait une réduction de la sévérité des troubles chez près des trois quarts d’entre eux.
Les années suivantes, Neurochlore a réalisé un essai monocentrique (2A), puis multicentrique (2B) dans 6 centres en France, sur près de 90 enfants, avant de signer en mars 2017 un accord de partenariat avec Servier ouvrant la voie à cet essai de phase 3.
« Les équipes de Neurochlore vont maintenant analyser en détail les résultats des études et potentiellement explorer de nouvelles approches basées sur l’intelligence artificielle qui pourraient permettre d’identifier des sous-populations de personnes atteintes de troubles du spectre autistique pour lesquelles la bumétanide serait active. L’hétérogénéité des TSA rend probablement impossible un traitement unique pour tous les enfants avec TSA », conclut le Pr Yehezkel Ben-Ari.
Une étude chinoise publiée en mars 2020 montrait encore des résultats encourageants, et émettait l’hypothèse d’un rôle clef de la bumétanide sur la réduction du taux du GABA (gamma-aminobutyric acid) dans le cerveau.
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Elevated androgenic and estrogenic unwanted aspect effects – exactly the things you
hope to keep away from by using SARMs. Whereas we don’t have anyplace close to the data and expertise we do
with steroid combinations, SARM users have discovered that combining SARMs with good synergy provides higher outcomes.
Nonetheless, it additionally increases side effects, relying on how potent the additional compound is.
It can mimic the features of ghrelin, which boosts IGF-1 and growth hormone
ranges.
RAD-140 is the more suppressive of those two compounds, so you must prepare your PCT plan for the tip of this cycle.
SARMs are diverse enough to be effectively used in all forms of cycles.
Select the best SARM or SARMs to incorporate in your cycle, at the right
dose, for the proper length of time, and optionally mix with appropriate and complimentary SARMs or different compounds.
You won’t get it good every time, however with patience and apply, you’ll quickly study to make use of SARMs in your goals.
Some users will take 50mg on the excessive
finish – however remember that Ibutamoren works very nicely at
decrease doses, so there isn’t any need or profit in leaping straight to a high dose with this compound.
If you’re going to run an Ibutamoren cycle, check out my full Ibutamoren (MK-677) cycle information. With a brief half-life of four hours, I find it better to separate the dose through
the day (morning, midday, late afternoon, and night) instead of taking it suddenly
to make sure it’s always active within the body.
Deca has low estrogenic properties however can nonetheless
cause some bloating, and one of many ways to reduce fluid buildup is to reduce back sodium and simple carbs in your diet whereas ingesting lots of water.
Deca-Durabolin is a slow-acting steroid, so positive aspects is
not going to come on quickly. To get the most effective results
and allow sufficient time for the steroid to promote
muscle positive aspects, a 16-week minimal cycle
is really helpful. In Contrast with many other steroids,
these gains should be prime quality and simpler to take care
of after a cycle. Test Enanthate is most commonly injected as quickly as
weekly; however, this frequency can enhance with larger doses.
So, Clen isn’t a fat loss miracle, but it’s a robust metabolic booster that will allow you
to burn calories sooner, and we all need to do
this in a cutting cycle. Clen is commonly stacked with potent cutting steroids like
Anavar or Winstrol and helps provide that further edge as you
work to turn out to be leaner throughout your slicing phase.
If you’re going to run a Clen cycle, check out my full Clenbuterol cycle guide.
This compound is confirmed to reduce body fats and enhance lean muscle.
Clen boosts the metabolic fee, which at its core is attributable to increased physique temperature
(this contributes to some possible aspect effects).
As I’ve already detailed, blasting for measurement and energy is sort
of similar to using Anadrol or Dianabol as a kickstart in longer cycles.
What might change is your training and food plan to tweak the
outcomes based on private objectives. You can’t go wrong with Dianabol or
Anadrol for a blasting phase or some other compounds talked about above for cutting
cycles. On the other hand, you can take a glance
at Anavar-only cycles as nicely as a deviation from using testosterone as the primary compound.
If you’re going to run an Anavar cycle, take a glance at my
full Anavar (Oxandrolone) cycle information. This time-frame also reduces
side effects, though this will closely depend upon what compounds
you’re utilizing. Medium cycles limit you from making
the features you want throughout these few weeks, so you’ll be pretty restricted to faster-acting compounds.
Testosterone Propionate is often the ester of selection for a medium cycle.
It Is taken orally, with a typical newbie cycle being
20mg/day for 4 weeks, adopted by post-cycle remedy.
With exhausting work and a strong quality bulking diet, features can exceed 20 lbs,
and water retention ought to be controllable. This is
a long-acting and slow-release steroid that, when utilized
in injection form, can last several months within the system.
Due to this sluggish exercise, its positive advantages could be very delayed and should not even start to be helpful until close to
the end of a normal-length steroid cycle. This makes Testosterone Undecanoate much less
sensible for many customers of performance-enhancing steroids compared with different
esters of testosterone. Thanks to its lower androgenic ranking, Deca
is among the few steroids men can tolerate – if not higher
– than testosterone itself. Deca-Durabolin usually causes less water retention than Testosterone Enanthate at
greater doses – but diet and individual response play a considerable function.
Other testosterone esters are faster-acting should you want quicker outcomes from a testosterone steroid.
At the lowest doses, you may be doing nothing greater
than offering a base stage of testosterone. Larger
efficiency doses at 400mg or extra per week are the
place the anabolic effects take impact, and desirable results
could be achieved. We all want to achieve muscle and lose fats simultaneously, and Testo-Max makes it potential
to just do that. Yes, you WILL need to be lean already earlier than beginning Testo-Max if you’d like the maximum muscle
hardness and vascularity it promotes while bulking and
adding uncooked lean muscle.
Anavar does not require injections and is taken orally
as a tablet, which is one other attractive benefit for those new to using steroids.
Deca is a superb selection for a protracted cycle the place the physique is regularly under stress and the place this compound will promote ligament, joint, and bone well being.
You can usually inject Deca just once per week and maintain stable ranges.
Useless to say, the highest purity and quality of Nandrolone decanoate you can acquire is pharmaceutical grade.
Black market pharmaceutical Deca-Durabolin exists, however you want to be sure you’re not purchasing
counterfeit products that may be of inferior high quality.
Individuals have been using Deca-Max for years, with
astonishing outcomes rivaling Nandrolone. Deca-Max offers
essentially the most ideal, secure, and LEGAL alternative to Nandrolone, and also you won’t be wasting any time or
money on combating nasty unwanted side effects. Nonetheless, including Arimidex or Aromasin for progesterone
is necessary for Deca as they work better at this job than Nolvadex.
Psychological unwanted effects are another sore level guys will frequently speak about.
Unreasonable ideas cause issues in relationships, while others wrestle with anxiety.
One Other severe risk is a discount of excellent levels of cholesterol that some customers have seen, even at very low doses.
Some hair loss can also happen as a result of ranges of DHT may be elevated.
SARMs goal androgen receptors in tissue that promote muscle
progress by stimulating anabolic activity in the bone and muscle11.
They work by being selective in the androgen receptors that
they bind to. At the same time, SARMs can avoid binding to receptors that trigger unwanted androgenic unwanted effects.
Primobolan (Metenolone) is one other in a protracted line of remarkable dihydrotestosterone (DHT) derived anabolic steroids.
It’s been mentioned that Primobolan was a favored
steroid used by Arnold Schwarzenegger in his prime,
and that is likely one of the causes it stays popular with bodybuilders right now.
Natural supplements work with out the risks that come with anabolic steroids.
Testosterone enanthate boosts testosterone levels common in other steroids.
It additionally causes fewer side effects, but liver toxicity could also be a concern.
References:
JBH News