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Ketamine Clinical Trial for Rett Syndrome Launches

March 13, 2019

You may have heard about a clinical trial testing ketamine in Rett Syndrome. We’re excited to be leading this important study and really asking in an unbiased way if ketamine can improve the symptoms of Rett Syndrome.

Ketamine is an old drug and has been studied in all kinds of areas - from anesthesia, where it was initially approved by FDA in 1970 (yes, that’s 50 years ago), to anxiety, pain relief, bi-polar disorder, obsessive-compulsive disorder, depression and others. You may have seen just recently that a nasal version of ketamine was approved by the FDA to treat depression. That means there is a lot of experience with ketamine over the years and due to its old age, we can be less concerned about unknown safety issues popping up.

Here’s why we’re excited. Ketamine is primarily considered an NMDA receptor antagonist (meaning it inhibits a receptor) but it also interacts with a lot of other receptors and signaling pathways in the brain that can change brain function. In addition to action in other neurological disorders, ketamine also shows symptom improvement in Rett mice as described in several publications, improving brain signaling, movement, and breathing. These mouse studies show that ketamine boosts key proteins needed for neuronal function in the absence of Mecp2 and that some changes in the brain persist after dosing is over. If the changes ketamine induces are retained beyond dosing, it raises interesting possibilities for effective intermittent or pulse-type dosing regimens.

Our excitement doesn’t stop there. We have also seen some interesting results in humans as well. One case report of a Rett patient receiving ketamine for seizure control had remarkable improvements in Rett symptoms that persisted for several weeks after a 5-day dosing regimen of oral ketamine, and a pilot study in 4 Rett patients receiving 4 different IV doses showed consistent improvements in breathing. We also hear the occasional yet repeated story where ketamine was administered as part of a procedure and families report notable changes in their child. However, not everyone has this experience. So what is really going on here? Well, that’s what we’re hoping to find out.

The goal of the study is to definitively answer the question of whether or not ketamine treatment leads to notable improvements in symptoms. We are testing ketamine dosed orally over a range of 4 doses below those that cause anesthesia. The study is designed as a cross-over, meaning that each patient will receive ketamine as well as placebo, so we can directly compare the responses to the two treatments in the same patient, and we can compare how all the patients who receive a particular dose respond, as well as patients across different doses. We decided to test the 5-day dosing regimen that was successful in the most encouraging case reported to date.

The study is double-blind and randomized, which means no one will know what treatment is being given during the study (not the participant or the study doctor or anyone involved in managing the study), and that the treatment order is randomly chosen by a computer for each patient. These conditions make the study conclusions stronger because no one rating the patient’s symptoms knows what treatment is being tested in that moment. It helps everyone focus on what is truly observed and prevents bias, whether conscious or unconscious.

What do we hope to accomplish? We are working closely with the FDA to ensure we conduct this study at the most rigorous standards for safety and efficacy with the goal to provide meaningful and interpretable data. At the end of the study we hope the study will confirm that ketamine is safe to administer to Rett patients and we also hope to say that ketamine dosed orally is or is not useful for managing Rett symptoms. If it is useful, we hope to know which doses are best suited for effective treatment. And if it is a good treatment, ketamine is already on the market so there would be no delays in getting access.

If you’re interested in helping to answer if ketamine is useful for individuals with Rett Syndrome, please check out the study on to learn more about patient eligibility requirements and what centers in the US are participating.