Effects of Creatine Supplementation in Rett Syndrome

Rett Syndrome Clinical Trial

Official title:

Effects of Creatine Supplementation in Rett Syndrome: A Randomized, Placebo-controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01147575
• Other study ID #: OENB11758
• Status: Completed
• Phase: N/A
• First received: June 17, 2010
• Last updated: June 18, 2010
• Start date: January 2005
• Est. completion date: January 2009

Study information

• Verified date: May 2010
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: January 2009
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 3 Years to 24 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Rett Syndrome
• Syndrome

Intervention

Dietary Supplement:
• Creatine monohydrate
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).
• Placebo
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).

Locations

Country	Name	City	State
Austria	Medical University Vienna, Dep. of Pediatric and Adolescent Medicine	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global DNA Methylation in serum	Global DNA methylation as one primary outcome measure is analyzed at time 0 and after 6 months.	6 months	No
Primary	Rett Syndrome Motor and Behavioral Assessment (RSMBA)		6 months	Yes
Secondary	Metabolic markers of methylation cycle	Markers: Methionine (µmol/l), Homocysteine (µmol/l), SAM (µmol/l), SAH (µmol/l)	6 months	No