Protective Role of Pre-/ Post-biotics on Gut Inflammation, Dysbiosis, and Life Quality in Rett Syndrome (Biotics_RTT) (Biotics_RTT)

  • STATUS
    Recruiting
  • days left to enroll
    81
  • participants needed
    30
  • sponsor
    Azienda Ospedaliera Universitaria Senese
Updated on 11 July 2022
seizure

Summary

The study will examine the potential efficacy and safety of two pre- and post-biotics on markers for gut inflammation and intestinal microbiota ecology in patients with Rett syndrome. Moreover, this trial will search for possible effects on epileptogenesis and quality of life.

Description

The gastrointestinal tract is the major site of exposure to environmental molecules where 1) dietary components are chemically transformed by the microbiota, and 2) gut-derived metabolites are disseminated to all organs, including the brain. The human gut microbiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Indeed, accumulating clinical and experimental evidences indicate that the gut microbiota impacts behavior, modulates neurotransmitter production in the gut and brain, influences brain development and myelination patterns. Specific gut-derived metabolites, such as 4-ethylphenyl sulfate (4-EPS) and isoamylamine (IAA) are known to alter brains activity and anxiety behavior in mice and/ or promoting neural cell death leading to cognitive decline. Rett syndrome (RTT; Online Mendelian Inheritance in Man, OMIM number #312750) is a severe and progressive neurological disorder that almost exclusively affects females with an incidence of ~1:10,000 live births. Loss-of-function mutations of the X-linked methyl-CpG binding protein 2 (MeCP2) gene is the major cause (approximately 90 %) of classical cases of RTT. Although a rare disorder, RTT represents a leading cause of severe cognitive impairment in the female gender. Affected individuals commonly show a period of apparent early normal development, followed by regression of hand and/or communication skills, and subsequent development of hand stereotypies, while gait is often abnormal in those who are learning to walk.

Despite a wide phenotypic variability, RTT is commonly associated with epilepsy, sleep disturbances, and gastrointestinal dysfunction thus suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota.

RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that MeCP2 loss-of-function can favour the establishment of a peculiar microbial community with altered production of short chain fatty acids (SCFAs) possibly contributing to the RTT gastrointestinal physiopathology.

Modulation of the systemic inflammatory response using pre- and post-biotics is advocated as a possible global therapeutic approach in neurological diseases such as Alzheimer's dementia.

Alpha-lactalbumin (ALAC), is the predominant whey protein in human milk, provides essential amino acids for protein synthesis in the developing neonates. Its supplementation in adults are associated with improved cognition, better memory and sleep. The bioactive properties of ALAC relate to antimicrobial activity, pre-biotic features and epithelial restoration via selective apoptosis activity. Moreover, the antibacterial peptides released from ALAC during digestion can exert immunostimulatory effects inducing phagocytic activity. Overall, ALAC shows reduction of inflammation and oxidative stress status as well as improvement of insulin resistance and increase in the synthesis of brain serotonin, a central nervous system neurotransmitter with well-known antiepileptic activity.

Butyrate, a bacterial metabolite and one of the main SCFAs, exhibits a broad range of pharmacological activities including microbiome modulating, anti-inflammatory, metabolic pathway regulating and anti-oxidant actions.

This body of knowledge supports testing pre- and post-biotics strategies for benefit in individuals with Rett syndrome with the goal of translating potential new treatments from experimental models to clinical practice. Results of this study could lead to the first approved pre- / post-biotics treatment for common co-morbidities in the disorder.

Details
Condition Rett Syndrome, Dysbiosis, Epilepsy, Quality of Life
Treatment ALAC, inulin, FOS, and sodium butyrate, Sodium butyrate and zinc oxide
Clinical Study IdentifierNCT05420805
SponsorAzienda Ospedaliera Universitaria Senese
Last Modified on11 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis of classic/typical Rett syndrome (and proven loss-of-function mutation of the MeCP2 gene) with gastrointestinal dysfunction and/or positive history of epilepsy
Female gender (age > / = 3 years old)
Ability to obtain written informed consent from their parent(s)/legal guardian(s)
Stable medications for at least 4 weeks prior to the baseline visit

Exclusion Criteria

Diagnosis not fitting into the Rett syndrome consensus guidelines
Nonpathogenic MECP2 mutation or mutations in non-MECP2 genes (i.e., cyclin-dependent kinase 5, CDKL5; forkhead box protein G1, FOXG1)
Male gender
Percutaneous endoscopic gastrostomy (PEG) tube
Proven hypersensitivity to one or more components of the dietary supplements (X-biotics)
Unstable concomitant medications less than 4 weeks prior to enrollment visit
Concomitant antibiotic therapy at the enrollment. In the case of antibiotic therapy, a 4-weeks washout period will be undertaken
Rejection of the informed consent form by the parents/caregivers and/or lack of compliance to the Study procedures
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note