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Effect of Uridine on GABA and High Energy Phosphate Levels in Healthy Volunteers (Uridine-GABA)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01261260
First received: December 14, 2010
Last updated: NA
Last verified: December 2010
History: No changes posted

December 14, 2010
December 14, 2010
November 2006
August 2008   (final data collection date for primary outcome measure)
Using MRI and MRS, after uridine administration an increase in brain GABA and NTP levels will be seen and increases in GABA and NTP will be correlated [ Time Frame: after 7 days of treatment ] [ Designated as safety issue: No ]
This choice of time period will allow a determination of time course to efficacy between the acute and extended ranges, and further, because therapeutic dosage levels of uridine have yet to be established, in this and future studies we hope to determine the optimal dosage at which uridine increases brain GABA and ß-NTP levels.
Same as current
No Changes Posted
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Effect of Uridine on GABA and High Energy Phosphate Levels in Healthy Volunteers
The Effect of Uridine on GABA and High Energy Phosphate Levels in Healthy Volunteers

On the dual basis of findings indicating GABA increases following acute and eight week SSRI/dopamine agonist administration and those indicating GABA-ergic effects following 14 day pyrimidine administration, the purpose of this study is to assess our following hypotheses:

  1. Relative to placebo, an oral dose of 1g of uridine BID for seven days will increase brain GABA levels in a sample of healthy, unmedicated adult males;
  2. Relative to placebo, an oral dose of 1g of uridine BID for seven days will increase NTP levels in a sample of healthy, unmedicated adult males; and
  3. Brain GABA levels will be directly correlated to high energy phosphate levels in this sample of healthy, unmedicated adult males.

Based on prior MRS studies by our group as well as the work of others, we hypothesize that oral administration of uridine will actuate an increase in brain gamma-amino butyric acid (GABA) levels, along with beta-nucleotide triphosphate (ß-NTP) levels, as compared with baseline. Our aim is to investigate this specific neuropharmacological effect and to demonstrate the suitability of a novel magnetic resonance spectroscopy protocol in so doing. Our rationale includes the consideration that the clinical utility of an intervention demonstrably effective in elevating brain GABA and high energy phosphate levels is broad, since lowered GABA and bioenergetic states are associated with a plurality of affective, anxiety, and substance use disorders.

On the dual basis of findings indicating GABA increases following acute and eight week SSRI/dopamine agonist administration and those noting GABA-ergic effects of 14 day pyrimidine administration, we hypothesize that an oral dose of 2g of uridine per day for seven days will increase brain GABA levels in a sample of healthy, unmedicated adult males. We also hypothesize that this 2g dose of uridine per day for 7 days will increase ß-NTP levels and, further, that the increase in GABA and high energy phosphate levels will be correlated. Of note, the phosphorylation of glutamic acid decarboxylase by ATP significantly increased the activity of this enzyme, which is reponsable for the synthesis of GABA. This choice of time period will allow a determination of time course to efficacy between the acute and extended ranges, and further, because therapeutic dosage levels of uridine have yet to be established, in this and future studies we hope to determine the optimal dosage at which uridine increases brain GABA and ß-NTP levels.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Healthy Male Subjects
Drug: Uridine
1 gram tablets BID for 7 days
Placebo Comparator: Uridine
1g BID
Intervention: Drug: Uridine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
33
August 2008
August 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male
  • Age range of 18-60 years
  • BMI between 18.5 and 28
  • Medication-free
  • Capable of providing informed consent
  • Non- smoking for a minimum of one year

Exclusion Criteria:

  • Meets DSM-IV criteria for any Axis I disorder (past or present)
  • Global assessment of functioning (DSM IV TR) less than 50
  • Age less than 18 or greater than 60
  • BMI lower than 18.5 or higher than 28
  • Any history of Alcohol or substance dependence or abuse according to DSM-IV criteria (except for caffeine dependence)
  • Any medical condition which in the opinion of the investigator may have an effect on mood symptoms
  • Any individual who has a current mood disturbance (as defined by DSM-IV-R criteria)
  • Use of cigarettes or other nicotine-containing products
  • Allergy or other contraindication to uridine
  • Individuals unable to comply with instructions or procedures of study
  • History of significant head trauma
  • Claustrophobia or other contraindication to MRI (e.g., pacemaker, metal fragments)
  • Any illicit substance use in the past thirty days
  • Any past treatment for substance abuse
  • Any past hospitalization for mental illness.
Male
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01261260
2005-P-002083-McLean, 2R01MH058681-04A2
No
Perry F. Renshaw MD PhD, Brain Institute, University of Utah
Mclean Hospital
National Institute of Mental Health (NIMH)
Principal Investigator: Perry F Renshaw, MD PhD The Brain Institute, University of Utah
Mclean Hospital
December 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP