Effects of Creatine Supplementation in Rett Syndrome
Condition: Rett Syndrome
MeSH terms: Rett Syndrome; Syndrome
Study type: Interventional

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.
    


Intervention name(s): Creatine monohydrate; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The patients received orally 200 mg CMH per kg body weight divided in three doses per day. Following period 1 (6 months) of supplementation and a wash-out period of 4 weeks without CMH the groups were switched for another 6 months (period 2).; The patients received orally 200 mg Placebo per kg body weight divided in three doses per day. Following period 1 (6 months) of supplementation and a wash-out period of 4 weeks without placebo the groups were switched for another 6 months (period 2).
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Rett Syndrome, Randomized, Methylation