Effects of Creatine Supplementation in Rett Syndrome

NCT ID: NCT01147575

Last Updated: 2010-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2009-01-31

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.

Conditions

Rett Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

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 respectively the groups were switched for another 6 months (period 2).

Group Type: ACTIVE_COMPARATOR

Creatine monohydrate

Intervention Type: DIETARY_SUPPLEMENT

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 in identically prepared capsules. Following period 1 (6 months) of supplementation and a wash-out period of 4 weeks without Placebo respectively the groups were switched for another 6 months (period 2).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

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).

Interventions

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).

Intervention Type: DIETARY_SUPPLEMENT

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).

Intervention Type: DIETARY_SUPPLEMENT

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 24 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Medical University Vienna, Department of Pediatric and Adolescent Medicine

Principal Investigators

Michael Freilinger, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University Vienna, Dep. Pediatrics

Locations

Medical University Vienna, Dep. of Pediatric and Adolescent Medicine

Vienna, , Austria

Countries

Austria

References

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.

Reference Type: DERIVED

PMID: 21654506 (View on PubMed)

Other Identifiers

OENB11758

Identifier Type: -

Identifier Source: org_study_id