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Neurobiology of a Mutation in Glycine Metabolism in Psychotic Disorders

This study has been completed.
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Deborah L. Levy, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01720316
First received: October 30, 2012
Last updated: September 18, 2017
Last verified: September 2017
Results First Received: April 16, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Schizo-affective Disorder
Bipolar Disorder
Interventions: Drug: Glycine
Drug: placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Glycine, Then Placebo One participant received glycine powder, up to 0.8 g/kg, administered with TID dosing for 6 weeks, then the participant received placebo TID dosing for 6 weeks, then the participant received open-label glycine for 6 weeks.
Placebo, Then Glycine One participant received placebo administered with TID dosing for 6 weeks, then the participant received glycine powder, up to 0.8 g/kg, TID dosing for 6 weeks, then the participant received open-label glycine for 6 weeks.

Participant Flow for 2 periods

Period 1:   Double-Blind Glycine Placebo Crossover
    Glycine, Then Placebo   Placebo, Then Glycine
STARTED   1   1 
COMPLETED   1   1 
NOT COMPLETED   0   0 

Period 2:   Open-label Glycine
    Glycine, Then Placebo   Placebo, Then Glycine
STARTED   1   1 
COMPLETED   1   1 
NOT COMPLETED   0   0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Glycine, Then Placebo One participant received glycine powder, up to 0.8 g/kg, administered with TID dosing for 6 weeks, then the participant received placebo TID dosing for 6 weeks, then open-label glycine for 6 weeks.
Placebo, Then Glycine One participant received placebo administered with TID dosing for 6 weeks, then the participant received glycine powder, up to 0.8 g/kg, TID dosing for 6 weeks, then open-label glycine for 6 weeks.
Total Total of all reporting groups

Baseline Measures
   Glycine, Then Placebo   Placebo, Then Glycine   Total 
Overall Participants Analyzed 
[Units: Participants]
 1   1   2 
Age [1] [2] 
[Units: Years]
Mean (Full Range)
     
age   59 [2]   32 [2]   45.5 
 (32 to 59) 
[1] age at beginning of study
[2] Single participant in each arm
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      1 100.0%      0   0.0%      1  50.0% 
Male      0   0.0%      1 100.0%      1  50.0% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      0   0.0%      0   0.0%      0   0.0% 
Not Hispanic or Latino      1 100.0%      1 100.0%      2 100.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0% 
Asian      0   0.0%      0   0.0%      0   0.0% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      0   0.0%      0   0.0%      0   0.0% 
White      1 100.0%      1 100.0%      2 100.0% 
More than one race      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0% 
Region of Enrollment 
[Units: Participants]
Count of Participants
     
United States   1   1   2 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Positive and Negative Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks During Intervention 1 (Glycine or Placebo), Intervention 2 (Glycine or Placebo), and During Open-label Glycine   [ Time Frame: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period and after each treatment period ]

2.  Primary:   Neurocognitive Function at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine   [ Time Frame: At baseline, during glycine treatment, during placebo treatment and during open-label glycine ]

3.  Primary:   Glycine Plasma Amino Acid Levels at Baseline, During Glycine Treatment, During Placebo Treatment and During Open-label Glycine   [ Time Frame: At baseline, during glycine treatment, during placebo treatment and during open-label glycine ]

4.  Primary:   Brief Psychiatric Rating Scale (BPRS) Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Positive and Negative Symptom Scores at Baseline and at 2, 4, and 6 Weeks During Intervention 1, Intervention 2, and During Open-label Glycine   [ Time Frame: baseline and at 2 weeks, 4 weeks, and 6 weeks within and after each treatment period ]

5.  Primary:   Clinical Global Impression (CGI) Severity Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period   [ Time Frame: CGI at baseline and at 2 weeks, 4 weeks, and 6 weeks per treatment period ]

6.  Primary:   Clinical Global Impression (CGI) Therapeutic Effect Scores at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period   [ Time Frame: at 2 weeks, 4 weeks, and 6 weeks within each treatment period ]

7.  Primary:   Mania Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period   [ Time Frame: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period ]

8.  Primary:   Depression Symptom Scores at Baseline and at 2 Weeks, 4 Weeks, and 6 Weeks Within Each Treatment Period   [ Time Frame: baseline and at 2 weeks, 4 weeks, and 6 weeks within each treatment period ]

9.  Secondary:   Brain Glycine/CR Ratio   [ Time Frame: baseline (pre-challenge, 60, 80, 100, 120 minutes post-challenge), and week 6 of glycine (pre-dose and 60, 80, 100, 120 minutes post-dose ]

10.  Secondary:   Brain Glutamate Metabolite Levels (Glutamate/Creatine Ratio: Glu/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT   [ Time Frame: baseline and week 6 of glycine ]

11.  Secondary:   Brain GABA Metabolite Levels (GABA/Creatine Ratio: GABA/Cr) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT   [ Time Frame: Baseline and week 6 of glycine ]

12.  Secondary:   Auditory Evoked Potentials in Latency (Msec) at BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF TREATMENT WITH GLYCINE   [ Time Frame: Recordings at baseline and week 6 of glycine ]

13.  Secondary:   Change in Magnocellular Pathway Function on Glycine Compared With Baseline. No Data Were Collected.   [ Time Frame: 6 weeks per treatment arm ]

14.  Secondary:   Auditory Evoked Potentials in Amplitude (Degrees Measured in Microvolts) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT   [ Time Frame: Recordings at baseline and week 6 of glycine ]

15.  Secondary:   Auditory Evoked Potentials in Gammas Oscillations (the Power Spectrum is Measured in Microvolts Squared) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT   [ Time Frame: Recordings at baseline and week 6 of glycine ]

16.  Secondary:   Auditory Evoked Potentials - P50 Ratio (P50 S2/P50 S1 Amplitude) at 1) BASELINE - Pre-glycine Treatment and 2) IN WEEK 6 OF GLYCINE TREATMENT   [ Time Frame: Recordings at baseline and week 6 of glycine ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Deborah L. Levy
Organization: McLean Hospital
phone: 617-855-2854
e-mail: dlevy@mclean.harvard.edu


Publications:
McCarthy SE, Makarov V, Kirov G, Addington AM, McClellan J, Yoon S, Perkins DO, Dickel DE, Kusenda M, Krastoshevsky O, Krause V, Kumar RA, Grozeva D, Malhotra D, Walsh T, Zackai EH, Kaplan P, Ganesh J, Krantz ID, Spinner NB, Roccanova P, Bhandari A, Pavon K, Lakshmi B, Leotta A, Kendall J, Lee YH, Vacic V, Gary S, Iakoucheva LM, Crow TJ, Christian SL, Lieberman JA, Stroup TS, Lehtimäki T, Puura K, Haldeman-Englert C, Pearl J, Goodell M, Willour VL, Derosse P, Steele J, Kassem L, Wolff J, Chitkara N, McMahon FJ, Malhotra AK, Potash JB, Schulze TG, Nöthen MM, Cichon S, Rietschel M, Leibenluft E, Kustanovich V, Lajonchere CM, Sutcliffe JS, Skuse D, Gill M, Gallagher L, Mendell NR; Wellcome Trust Case Control Consortium, Craddock N, Owen MJ, O'Donovan MC, Shaikh TH, Susser E, Delisi LE, Sullivan PF, Deutsch CK, Rapoport J, Levy DL, King MC, Sebat J. Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet. 2009 Nov;41(11):1223-7. doi: 10.1038/ng.474. Epub 2009 Oct 25.


Responsible Party: Deborah L. Levy, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01720316     History of Changes
Other Study ID Numbers: 2012p001597
R21MH097470-01A1 ( U.S. NIH Grant/Contract )
Study First Received: October 30, 2012
Results First Received: April 16, 2017
Last Updated: September 18, 2017