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Effects of Creatine Supplementation in Rett Syndrome

This study has been completed.
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01147575
First received: June 17, 2010
Last updated: June 18, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention
Rett Syndrome
Dietary Supplement: Creatine monohydrate
Dietary Supplement: Placebo

Study Type: Interventional
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
Official Title: Effects of Creatine Supplementation in Rett Syndrome: A Randomized, Placebo-controlled Trial

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Global DNA Methylation in serum [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Global DNA methylation as one primary outcome measure is analyzed at time 0 and after 6 months.

  • Rett Syndrome Motor and Behavioral Assessment (RSMBA) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Metabolic markers of methylation cycle [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Markers: Methionine (µmol/l), Homocysteine (µmol/l), SAM (µmol/l), SAH (µmol/l)


Enrollment: 21
Study Start Date: January 2005
Study Completion Date: January 2009
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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).
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).
Other Name: Creatine monohydrate
Placebo Comparator: 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).
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).

  Eligibility

Ages Eligible for Study:   3 Years to 24 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01147575

Locations
Austria
Medical University Vienna, Dep. of Pediatric and Adolescent Medicine
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Michael Freilinger, MD Medical University Vienna, Dep. Pediatrics
  More Information

No publications provided by Medical University of Vienna

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M Freilinger, MD, Medical University Vienna, Department of Pediatric and Adolescent Medicine
ClinicalTrials.gov Identifier: NCT01147575     History of Changes
Other Study ID Numbers: OENB11758
Study First Received: June 17, 2010
Last Updated: June 18, 2010
Health Authority: Austria: Ethikkommission

Keywords provided by Medical University of Vienna:
Rett Syndrome, Randomized, Methylation

Additional relevant MeSH terms:
Rett Syndrome
Syndrome
Disease
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Mental Retardation, X-Linked
Nervous System Diseases
Neurobehavioral Manifestations
Neurodegenerative Diseases
Neurologic Manifestations
Pathologic Processes

ClinicalTrials.gov processed this record on November 19, 2014