L-arginine Study for Persistent Symptoms of Schizophrenia

NCT04054973 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: H00017202
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to see if daily combination treatment of L-arginine and Kuvan changes brain chemistry in people experiencing schizophrenia as measured by MRS brain scans.

Conditions

Schizo Affective Disorder; Schizophrenia

Keywords

psychosis; Treatment resistant; L-arginine; MRS

Outcome Measures

Primary Outcomes (2)

• Changes in brain chemistry as measured by 1H-MRS scans

  To demonstrate that L-arginine and tetrahydrobiopterin (BH4) combination targets and alters brain chemistry in patients with TRS (target engagement). The investigators hypothesize that two-week treatment of L-arginine and Tetrahydrobiopterin (as Kuvan) will alter glutamate and GABA levels measured with proton magnetic resonance spectroscopy (1H-MRS).

  14 days

• Incidence of Treatment-Emergent Adverse Events as assessed by patient report

  The study doctor in conjunction with the study coordinator will conduct a diagnostic interview with the subject at each visit to record the incidence of treatment-emergent adverse events as assessed by patient report.

  14-days

Secondary Outcomes (5)

• Change in Positive and Negative Symptom scale (PANSS) from Baseline to Day 14

  14 days

• Evaluate changes in NO bioavailability in breath from Baseline to Day 14

  14 days

• Change in blood levels of glutathione (GSH) from baseline to day 14.

  14 days

• Change in blood levels of high-sensitivity C reactive protein (hsCRP) from baseline to day 14.

  14 days

• Change in blood levels of Tumor Necrosis Factor (TNF-α) from baseline to day 14.

  14 days

Study Arms (1)

L-arginine and Kuvan

EXPERIMENTAL

Open-label single arm study, all participants will be in this group

Drug: L-arginine; Drug: Sapropterin Dihydrochloride

Interventions

L-arginine DRUG

6000mg of L-arginine daily for 14 days

L-arginine and Kuvan

Sapropterin Dihydrochloride DRUG

800mg of Kuvan daily for 14 days

Also known as: Kuvan

L-arginine and Kuvan

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or Females aged 18-65 years inclusive.
• English speaking.
• Primary diagnosis of Schizophrenia established by a structured psychiatric evaluation (MINI) based on Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) criteria.
• Written informed consent in compliance with 21 CFR part 50 and in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines.
• A Positive and Negative Syndrome Scale (PANSS) (Kay et al 1987) total score ≥ 70 with a score of \> 4 on two or more of the following PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content.
• A score of ≥4 on the Clinical Global Impression-Severity (CGI-S) (Guy, 1976).
• Must have ongoing antipsychotic treatment for at least 8 weeks, with a stable dose for at least 4 weeks. Antipsychotic medication will not be modified by the research team during the subject's enrollment or participation.
• Subjects who have failed to achieve clinically-recognized symptom reduction to at least 1 marketed antipsychotic agent, given at a Physician Desk Reference (PDR)-defined therapeutic dose for ≥ 8 weeks during the past 12 months, will be eligible.
• Women of childbearing potential must have a negative pregnancy test performed at screening visit prior to randomization. Women enrolled in this trial must use adequate birth control.
• Understands and is able, willing, and (in the opinion of the investigator) likely to fully comply with the study procedures and restrictions.

You may not qualify if:

• Subjects with a history of renal insufficiency, congestive heart failure, cardiac arrhythmias or history of myocardial infarction, liver cirrhosis, guanidinoacetate methyltransferase deficiency, herpes.
• Subjects who are non-English speaking.
• Subjects with any clinically significant abnormalities as determined by medical history, physical exam, clinical and lab evaluation suggestive of an underlying disease state that may, in the opinion of the investigator, confound the results of study, increase risk to the subject, or lead to difficulty complying with the protocol.
• On medications known to inhibit folate metabolism (e.g., methotrexate).
• On medications known to affect NO-mediated vaso-relaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil).
• Subjects on nitrates.
• Subjects on levodopa.
• Subjects on antihypertensive medications (such as ACE inhibitors, angiotensin receptor blockers, isoproterenol, potassium-sparing diuretics).
• Subjects on antidiabetes medications.
• Subjects on anticoagulant/antiplatelet medications.
• Subjects with a current (within the last 3 months) DSM-V diagnosis of alcohol or substance use disorder (excluding nicotine and caffeine) as established by the clinical assessment (MINI) at the screening visit will be excluded.
• Tested positive for the urine drug screen.
• Subjects at imminent risk of suicide or injury to self or others, as per the opinion of the investigator, or history of significant suicide attempt within the last 6 months as per the Columbia Suicide Severity Rating Scale (C-SSRS).
• Subjects that have taken an investigational drug or taken part in a clinical trial within 30 days prior to screening.
• Known history of phenylketonuria (PKU).

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead

Study Sites (1)

UMass Medical School

Worcester, Massachusetts, 01655, United States

Location

MeSH Terms

Conditions

Psychotic Disorders; Schizophrenia

Interventions

Arginine; sapropterin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Xiaoduo Fan

  UMass Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Psychotic Disorders Program

Model Details: Open-label single arm pilot trial of L-arginine and Kuvan combination therapy

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: August 13, 2019
• Study Start: September 11, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: January 20, 2022

Record last verified: 2022-01

Locations

US (1)