L-arginine Study for Persistent Symptoms of Schizophrenia

NCT ID: NCT04054973

Last Updated: 2022-01-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-11
• Study Completion Date: 2021-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

L-arginine and Kuvan

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

Group Type: EXPERIMENTAL

L-arginine

Intervention Type: DRUG

6000mg of L-arginine daily for 14 days

Sapropterin Dihydrochloride

Intervention Type: DRUG

800mg of Kuvan daily for 14 days

Interventions

L-arginine

6000mg of L-arginine daily for 14 days

Intervention Type: DRUG

Sapropterin Dihydrochloride

800mg of Kuvan daily for 14 days

Intervention Type: DRUG

Other Intervention Names

Kuvan

Eligibility Criteria

Inclusion Criteria

1. Males or Females aged 18-65 years inclusive.

2. English speaking.

3. 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.

4. 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.

5. 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.

6. A score of ≥4 on the Clinical Global Impression-Severity (CGI-S) (Guy, 1976).

7. 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.

8. 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.

9. 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.

10. Understands and is able, willing, and (in the opinion of the investigator) likely to fully comply with the study procedures and restrictions.

Exclusion Criteria

1. Subjects with a history of renal insufficiency, congestive heart failure, cardiac arrhythmias or history of myocardial infarction, liver cirrhosis, guanidinoacetate methyltransferase deficiency, herpes.

2. Subjects who are non-English speaking.

3. 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.

4. Subjects with the lab values defined as exclusionary safety values in Table 1.

5. On medications known to inhibit folate metabolism (e.g., methotrexate).

6. On medications known to affect NO-mediated vaso-relaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil).

7. Subjects on nitrates.

8. Subjects on levodopa.

9. Subjects on antihypertensive medications (such as ACE inhibitors, angiotensin receptor blockers, isoproterenol, potassium-sparing diuretics).

10. Subjects on antidiabetes medications.

11. Subjects on anticoagulant/antiplatelet medications.

12. 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.

13. Tested positive for the urine drug screen.

14. 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).

15. Subjects that have taken an investigational drug or taken part in a clinical trial within 30 days prior to screening.

16. Known history of phenylketonuria (PKU).

17. Known hypersensitivity reactions (such as anaphylaxis and rash) to L-arginine and/or BH4.

18. Any other reason that, in the opinion of the investigator, would compromise patient safety or integrity of the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Massachusetts, Worcester

OTHER

Sponsor Role: lead

Responsible Party

Xiaoduo Fan

Director, Psychotic Disorders Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiaoduo Fan

Role: PRINCIPAL_INVESTIGATOR

UMass Medical School

Locations

UMass Medical School

Worcester, Massachusetts, United States

Countries

United States

Other Identifiers

H00017202

Identifier Type: -

Identifier Source: org_study_id