Clinical trial NCT01147575: Effects of Creatine Supplementation in Rett Syndrome
Official title: Effects of Creatine Supplementation in Rett Syndrome: A Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rett Syndrome
Keywords: Rett Syndrome, Randomized, Methylation
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2010-06-22
Enrollment: 21
Sex: FEMALE
Minimum age (years): 3
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Creatine supplementation in RTT: a randomized controlled trial

Rett Syndrome (RTT) is a neurodevelopmental disorder characterised by apparently normal early development (stage 1 of RTT) followed by loss of purposeful hand use, distinctive hand stereotypes, slow brain growth, loss of language, respiratory irregularities, gastrointestinal disturbances, gait abnormalities, seizures, and mental retardation. These symptoms typically appear between 6 and 18 months of age (stage 2). Subsequently, there is gradual stabilisation of severe mental retardation and motor compromise (stage 3). The majority (70% to 80%) of patients show mutations in the methyl-CpG-binding-protein-2 (MeCP2) gene, located on chromosome Xq28. MeCP2 encodes a transcription repressor protein that is ubiquitously expressed in all tissues.

As RTT primarily affects females, only very few males with mutations in MeCP2 have been identified. Mutations in MeCP2 have also been identified in children with X-linked mental retardation, autism and a clinical phenotype that resembles Angelman Syndrome.

The aim of this study is to investigate the effects of a dietary supplement on the biochemical and clinical parameter of RTT. About 80 % of labile methyl groups generated through the re-methylation cycle are used for the synthesis of creatine within the human organism. Supplementation of creatine will therefore increase the availability of labile methyl groups for different methylation reactions including methylation of DNA.

The study will be double blind and cross-over. The patients will get creatine monophosphate (200 mg/kg/d in three dosages per day) or placebo. After 6 months and a wash-out period of 4 weeks the groups are changed for the next 6 months.

All participants with RTT and mutations in MeCP2 will undergo physical and neurological exam, quantitative EEG, behavioral assessment, laboratory testing, and neuropsychological evaluations. Participants will have a follow-up after 3, 6, 10, 13 and 16 months (3 months after finishing the study), which will include similar assessments.


Eligibility criteria: Inclusion Criteria:

* RTT Syndrome, diagnosed by current consensus criteria

Exclusion Criteria:

* taking supplements containing either folic acid or vitamin B12 or knowingly consuming any vitamin-fortified food items

Primary outcomes:
measure: Global DNA Methylation in serum
timeFrame: 6 months
measure: Rett Syndrome Motor and Behavioral Assessment (RSMBA)
timeFrame: 6 months
Secondary outcomes:
measure: Metabolic markers of methylation cycle
timeFrame: 6 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University Vienna, Dep. of Pediatric and Adolescent Medicine
Study officials:
affiliation: Medical University Vienna, Dep. Pediatrics
name: Michael Freilinger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Freilinger M, Dunkler D, Lanator I, Item CB, Muhl A, Fowler B, Bodamer OA. Effects of creatine supplementation in Rett syndrome: a randomized, placebo-controlled trial. J Dev Behav Pediatr. 2011 Jul-Aug;32(6):454-60. doi: 10.1097/DBP.0b013e31822177a8.