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Tryptophan MRI in People With Schizophrenia and Healthy Controls

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ClinicalTrials.gov Identifier: NCT02067975
Recruitment Status : Recruiting
First Posted : February 20, 2014
Last Update Posted : May 16, 2017
Sponsor:
Collaborators:
Mitsubishi Tanabe Pharma Corporation
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Robert W. Buchanan, University of Maryland

Brief Summary:
Kynurenic acid (KYNA) is a naturally occurring chemical in the brain. Studies with rodents indicate that levels of KYNA can impact levels of the neurotransmitters glutamate and dopamine. One way to reliably increase KYNA levels is by ingesting the amino acid tryptophan. Tryptophan is a normal part of the human diet. Tryptophan gets metabolized/changed to other chemicals in the body- including KYNA. By giving people 6 grams of tryptophan, the investigators will be able to increase the KYNA level in a controlled way. The investigators will then be able to study the effects of KYNA on neurotransmitters by using cognitive tests and magnetic resonance imaging techniques (measuring brain activity and brain chemistry using the MRI magnet). They will test people using tryptophan and also using a placebo to look for differences. The investigators will test healthy controls and people with schizophrenia to look for differences.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Tryptophan Drug: Placebo Phase 2 Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Neuroimaging of Tryptophan Challenge in People With Schizophrenia and Healthy Controls
Study Start Date : September 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Tryptophan
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: tryptophan
6gm of tryptophan at least two weeks apart at time zero of 7 hour visits 2 and 3
Drug: Tryptophan
Placebo Comparator: Placebo
Placebo will be a liquid drink without tryptophan. 6mg at least two weeks apart at time zero of the 7 hour visits 2 and 3.
Drug: Placebo



Primary Outcome Measures :
  1. Visual memory, attention, and processing speed scores on the Relational and Item Specific Encoding Task (RISE). [ Time Frame: at least two weeks ]
    Tryptophan-induced elevated KYNA levels transiently impair performance on neuropsychological measures of verbal and visual memory, attention, and processing speed.


Secondary Outcome Measures :
  1. Dorsolateralhippcampal fMRI activation and connectivity using the Relational and Item Specific Encoding Task (RISE). [ Time Frame: at least two weeks ]
    Tryptophan-induced elevated KYNA levels alters dorsolateralhippcampal fMRI activation and connectivity during the performance of the relational memory task RISE.


Other Outcome Measures:
  1. Glutamate levels using fMRI [ Time Frame: at least two weeks ]
    Tryptophan-induced elevated KYNA levels alter 1H-MRS measures of glutamate levels in the medial prefrontal cortex (mPFC), a brain region involved in attention and processing speed behaviors, default mode network activity, and sensitive to changes in KYNA levels.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (Schizophrenia:

  • Males and females between the ages of 18 and 55 years
  • Has met DSM-IV-TR/DSM-5 Criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder
  • Prescription of antipsychotic medication for at least 60 days and constant dose for 30 days prior to study entry (either first or second generation antipsychotics permitted)
  • Women must be in the first half of their menstrual cycle at the time of the 2 challenge visits

Inclusion Criteria (Healthy Controls):

  • Males and females between the ages of 18 and 55 years
  • No DSM-IV-TR/DSM-5 Axis I Disorder (documented by SCID)
  • Women must be in the first half of their menstrual cycle at the time of the 2 challenge visits

Exclusion Criteria:

  • DSM-IV-TR/DSM-5 substance abuse in the last month or substance dependence in the last 6 months (documented by SCID)
  • Calgary Depression Scale total score ≥ 10 at baseline
  • Current smoker (expired CO ≥ 10 ppm)
  • Current use of nicotine replacement therapy or other nicotine products
  • Pregnancy or breast feeding
  • Post-menopausal women will not be included due to changes in the HPA axis expression and hormonal effects on cognition. In women over the age of 45, menopausal status will be evaluated clinically
  • Excessive self-reported daily caffeine intake, defined as intake exceeding 1000 mg or the equivalent of 8 cups of coffee
  • Active disorders that have been reported to affect tryptophan metabolism or interfere with absorption will be excluded (Acute Intermittent Porphyria, Celiac Disease, Crohn's Disease, Irritable Bowel Syndrome
  • History of an organic brain disorder; mental retardation; or a medical condition, whose pathology or treatment could alter cognition
  • Claustrophobia
  • Metal in body that will interfere with MR imaging
  • Treatment with monoamine oxidase inhibitors, migraine headache medications (triptans) and dextromethorphan

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02067975


Contacts
Contact: Catherine Kilday 410-402-6412 ckilday@mprc.umaryland.edu

Locations
United States, Maryland
Maryland Psychiatric Research Center Recruiting
Catonsville, Maryland, United States, 21228
Principal Investigator: Robert W. Buchanan, M.D.         
Sponsors and Collaborators
University of Maryland
Mitsubishi Tanabe Pharma Corporation
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Robert W Buchanan, M.D. University of Maryland

Responsible Party: Robert W. Buchanan, Interim Director, University of Maryland
ClinicalTrials.gov Identifier: NCT02067975     History of Changes
Other Study ID Numbers: HP-00057861
1P50MH103222-01 ( U.S. NIH Grant/Contract )
First Posted: February 20, 2014    Key Record Dates
Last Update Posted: May 16, 2017
Last Verified: May 2017

Keywords provided by Robert W. Buchanan, University of Maryland:
tryptophan
kynurenic acid
schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Tryptophan
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs