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

NCT05420805 | Completed

• 1 other identifier: NCT
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rett Syndrome; Dysbiosis; Epilepsy; Quality of Life

Keywords

Gut dysfunction; Inflammation; Alpha-lactalbumin; Butyrate

Outcome Measures

Primary Outcomes (3)

• Systemic inflammation

  Change in circulating pro-inflammatory or change in anti-inflammatory cytokine levels

  Change at 3 months from baseline of each interventional arm

• Gut inflammation

  Change in fecal calprotectin levels

  Change at 3 months from baseline of each interventional arm

• Gut dysbiosis

  Change in intestinal microbiota biodiversity

  Change at 3 months from baseline of each interventional arm

Secondary Outcomes (1)

• Epileptogenesis

  Change at 3 months from baseline of each interventional arm

Other Outcomes (2)

• Quality of life and gastrointestinal health

  Change at 3 months from baseline of each interventional arm

• Quality of life and illness severity

  Change at 3 months from baseline of each interventional arm

Study Arms (2)

Pre- and post-biotic (ALAC, inulin, FOS, and sodium butyrate)

ACTIVE COMPARATOR

The product (ALAC+butyrate+inulin+fructo oligosaccharides FOS) is a powder for oral suspension. Dosage is dependent on weight. For participants weighing \<50 kg, a 4 g dose (i.e., one 4 g sachet) is intended to be administered orally once a day after dissolving in water. For participants weighing ≥50 kg, a 4 g dose (i.e., 4 g sachets) is intended to be administered orally twice a day (12h interval) after dissolving in water.

Dietary Supplement: ALAC, inulin, FOS, and sodium butyrate

Post-biotic (sodium butyrate and zinc oxide)

ACTIVE COMPARATOR

The product (sodium butyrate+ zinc oxide) is in the form of tablets. Dosage is dependent on weight. For participants weighing \<25 kg, one 380 mg tablet is intended to be administered orally twice a day . For participants weighing 25 to 40 kg, three 380 mg tablet dose is intended to be administered orally according to the 2+1 tablets per day schedule (12h interval). For participants weighing ≥40 kg, four 380 mg tablet dose is intended to be administered orally according to the 2+2 tablets per day schedule (12h interval).

Dietary Supplement: Sodium butyrate and zinc oxide

Interventions

ALAC, inulin, FOS, and sodium butyrate DIETARY_SUPPLEMENT

Pre- and post-biotic supplementation will be administered for 3 month period (i.e. 12 weeks) given the filling out of a supplementation diary by parents/caregivers. At the scheduled visits/ phone contacts (i.e., baseline, 4 weeks and 12 weeks), systemic inflammation, intestinal inflammation, and gut microbiome characterization as well as treatment compliance, clinical and dietary intake will be assessed. A seizure diary will be provided to parents/caregivers in order to check the frequency and entity of the critical episodes. An EEG recording will be performed at enrollment (or within 6 months prior to the baseline visit).

Pre- and post-biotic (ALAC, inulin, FOS, and sodium butyrate)

Sodium butyrate and zinc oxide DIETARY_SUPPLEMENT

Post-biotic supplementation will be administered for 3 month period (i.e. 12 weeks) given the filling out of a supplementation diary by parents/caregivers. At the scheduled visits/ phone contacts (i.e., baseline, 4 weeks and 12 weeks), systemic inflammation, intestinal inflammation, and gut microbiome characterization, as well as treatment compliance, clinical and dietary intake will be assessed. A seizure diary will be provided to parents/caregivers in order to check the frequency and entity of the critical episodes. An EEG recording will be performed at enrollment (or within 6 months prior to the baseline visit).

Post-biotic (sodium butyrate and zinc oxide)

Eligibility Criteria

• Age: 3 Years+
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Senese: lead
• Kolfarma s.r.l. - Italy: collaborator
• European Institute of Oncology: collaborator

Study Sites (1)

Policlinico "S. Maria alle Scotte" Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

MeSH Terms

Conditions

Rett Syndrome; Dysbiosis; Epilepsy; Inflammation

Interventions

Inulin; Butyric Acid; Zinc Oxide

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Oxides; Oxygen Compounds; Inorganic Chemicals; Zinc Compounds

Study Officials

• Claudio De Felice, MD

  Policlinico "S. Maria alle Scotte" Azienda Ospedaliera Universitaria Senese , 53100 Siena, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double (Investigator, Outcomes Assessor)
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a 29-week pilot, single site, randomized, cross-over trial of alpha-lactalbumin + sodium butyrate + inulin + fructo-oligosaccharides vs. sodium butyrate + zinc oxide. Periods I and II of the randomized study are 12 weeks long together with a 4 week washout period.

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 15, 2022
• Study Start: April 1, 2022
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)