Tryptophan MRI in People With Schizophrenia and Healthy Controls

NCT02067975 | Completed Phase 2 Results DMC

• 2 other identifiers: HP-000578611P50MH103222-01
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Keywords

tryptophan; kynurenic acid; schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change in Verbal Memory Scores From Baseline to 4 Hours Post-Treatment

  The following assessment was used to assess the outcome measure: the Hopkins Verbal Learning Test-Revised (HVLT-R). HVLT total scores range from 0 to 36. In order to conduct group comparisons, the HVLT raw total scores are converted to a t-score (range: -10 to 80). The mean t-scores for each condition are below (see outcome measure data table). Higher scores represent better performance. Participants performed the same task before pre- and post-treatment with Tryptophan and again with placebo (2 weeks between conditions). Change in scores pre- and post-treatment were compared between the Tryptophan and placebo conditions.

  The order in which participants received either the tryptophan or placebo was randomized. The HVLT was administered 90 minutes prior to treatment and 4 hours post treatment. There were at least two weeks between the challenge days.

Study Arms (2)

Healthy Controls

OTHER

All participants will receive both 6gm of tryptophan at least two weeks apart at time zero of 7 hour visits 2 and 3, and will also receive 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. The order in which participants receive either placebo or tryptophan will be randomized (ie. placebo first study visit day tryptophan on second study day, or tryptophan on first study day and placebo on second study day)

Drug: Tryptophan; Drug: Placebo

Schizophrenia Related Disorders

OTHER

All participants will receive both 6gm of tryptophan at least two weeks apart at time zero of 7 hour visits 2 and 3, and will also receive 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. The order in which participants receive either placebo or tryptophan will be randomized (ie. placebo first study visit day tryptophan on second study day, or tryptophan on first study day and placebo on second study day)

Drug: Tryptophan; Drug: Placebo

Interventions

Tryptophan DRUG

Healthy Controls; Schizophrenia Related Disorders

Placebo DRUG

Healthy Controls; Schizophrenia Related Disorders

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Tanabe Pharma Corporation: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Maryland Psychiatric Research Center

Catonsville, Maryland, 21228, United States

Location

Related Publications (1)

• Hare SM, Adhikari BM, Mo C, Chen S, Wijtenburg SA, Seneviratne C, Kane-Gerard S, Sathyasaikumar KV, Notarangelo FM, Schwarcz R, Kelly DL, Rowland LM, Buchanan RW. Tryptophan challenge in individuals with schizophrenia and healthy controls: acute effects on circulating kynurenine and kynurenic acid, cognition and cerebral blood flow. Neuropsychopharmacology. 2023 Oct;48(11):1594-1601. doi: 10.1038/s41386-023-01587-3. Epub 2023 Apr 28.

  PMID: 37118058 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Tryptophan

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Sam Kane-Gerard
• Organization: Maryland Psychiatric Research Center

SGerard@som.umaryland.edu

410-402-6120

Study Officials

• Robert W Buchanan, M.D.

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: February 11, 2014
• First Posted: February 20, 2014
• Study Start: August 14, 2014
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: July 30, 2024
• Results First Posted: August 26, 2021

Record last verified: 2024-07

Locations

US (1)