Schizo Affective DisorderPhase 2NCT04054973
L-arginine Study for Persistent Symptoms of Schizophrenia
A Phase 2 study testing L-arginine and Sapropterin Dihydrochloride in people with Schizo Affective Disorder and Schizophrenia, run by University of Massachusetts, Worcester at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizo Affective Disorder, Schizophrenia
- What is being tested?
- L-arginine and Sapropterin Dihydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Sep 2019to 31 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
- Subjects with the lab values defined as exclusionary safety values in Table 1.
- 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).
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- 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).
- Known hypersensitivity reactions (such as anaphylaxis and rash) to L-arginine and/or BH4.
- Any other reason that, in the opinion of the investigator, would compromise patient safety or integrity of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
UMass Medical School
Worcester, Massachusetts, 01655
About this study
Official title: An Open-label Feasibility Trial of Adjunctive L-arginine and Tetrahydrobiopterin Combination in Patients With Treatment Resistant Schizophrenia
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
- Being tested
- L-arginine, Sapropterin Dihydrochloride
- Keywords
- psychosis, Treatment resistant, L-arginine, MRS
- Medical subject headings
- Psychotic Disorders, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginineDrug
6000mg of L-arginine daily for 14 days
Sapropterin DihydrochlorideDrug
Also called Kuvan
800mg of Kuvan daily for 14 days
| Study group | Role | What they receive |
|---|---|---|
| L-arginine and Kuvan | Experimental | Open-label single arm study, all participants will be in this group Receives: Drug: L-arginine; Drug: Sapropterin Dihydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 14-days
Secondary outcomes (5)
Change in Positive and Negative Symptom scale (PANSS) from Baseline to Day 14
The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at until day 14.
Measured: 14 days
Evaluate changes in NO bioavailability in breath from Baseline to Day 14
Will measure change in NO bioavailability in breath using a Sievers NO Analyzer (NOA280i).
Measured: 14 days
Change in blood levels of glutathione (GSH) from baseline to day 14.
Blood levels of glutathione (GSH) (uM) will be measured at baseline and day 14 via blood draw. Values of the this biomarker correspond to the bodies inflammatory and oxidative stress response. The results will be analyzed and compared from baseline to day 14 to measure for the effect of L-arginine and BH4 combination treatment on the body's inflammatory and oxidative stress response regulation.
Measured: 14 days
Change in blood levels of high-sensitivity C reactive protein (hsCRP) from baseline to day 14.
Blood levels of high-sensitivity C reactive protein (hsCRP) (mg/L) will be measured at baseline and day 14 via blood draw. Values of the this biomarker correspond to the bodies inflammatory and oxidative stress response. The results will be analyzed and compared from baseline to day 14 to measure for the effect of L-arginine and BH4 combination treatment on the body's inflammatory and oxidative stress response regulation.
Measured: 14 days
Change in blood levels of Tumor Necrosis Factor (TNF-α) from baseline to day 14.
Blood levels of Tumor Necrosis Factor (TNF-α) (pg/mL) will be measured at baseline and day 14 via blood draw. Values of the this biomarker correspond to the bodies inflammatory and oxidative stress response. The results will be analyzed and compared from baseline to day 14 to measure for the effect of L-arginine and BH4 combination treatment on the body's inflammatory and oxidative stress response regulation.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2019
- Study start11 Sep 2019
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Why it stopped: Study was unable to be started due to unavailability of study medication.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizo Affective DisorderStudies of the same condition, open and under way.
- More trials run by University of Massachusetts, WorcesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label single arm pilot trial of L-arginine and Kuvan combination therapy
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Worcester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiaoduo Fan, University of Massachusetts, Worcester
- Investigators
- Xiaoduo Fan, Principal investigator, UMass Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04054973
- Sponsor's protocol ID
- H00017202
- Status last verified
- Jan 2022
- First submitted
- 2 Aug 2019
- Last updated
- 20 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Feasibility Trial of Adjunctive L-arginine and Tetrahydrobiopterin Combination in Patients With Treatment Resistant Schizophrenia
- ClinicalTrials.gov ID
- NCT04054973
- Acronym / sponsor ID
- H00017202
- Conditions
- Schizo Affective Disorder, Schizophrenia
- Keywords
- psychosis, Treatment resistant, L-arginine, MRS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was unable to be started due to unavailability of study medication.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Massachusetts, WorcesterUniversity, hospital or other
- Study start
- 11 Sep 2019 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 13 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label single arm pilot trial of L-arginine and Kuvan combination therapy
| Arm | Type | Receives |
|---|---|---|
| L-arginine and Kuvan | Experimental | Drug: L-arginine, Drug: Sapropterin DihydrochlorideOpen-label single arm study, all participants will be in this group |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
- Subjects with the lab values defined as exclusionary safety values in Table 1.
- On medications known to inhibit folate metabolism (e.g., methotrexate).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-arginine6000mg of L-arginine daily for 14 days | Drug | L-arginine and Kuvan |
| Sapropterin DihydrochlorideAlso: Kuvan800mg of Kuvan daily for 14 days | Drug | L-arginine and Kuvan |
Primary outcome
Changes in brain chemistry as measured by 1H-MRS scans
Time frame: 14 days
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).
Incidence of Treatment-Emergent Adverse Events as assessed by patient report
Time frame: 14-days
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.
5 secondary outcomes
Change in Positive and Negative Symptom scale (PANSS) from Baseline to Day 14
Time frame: 14 days
Evaluate changes in NO bioavailability in breath from Baseline to Day 14
Time frame: 14 days
Change in blood levels of glutathione (GSH) from baseline to day 14.
Time frame: 14 days
Change in blood levels of high-sensitivity C reactive protein (hsCRP) from baseline to day 14.
Time frame: 14 days
Change in blood levels of Tumor Necrosis Factor (TNF-α) from baseline to day 14.
Time frame: 14 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaoduo Fan principal investigator
UMass Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L-arginine and Sapropterin Dihydrochloride in people with Schizo Affective Disorder and Schizophrenia, run by University of Massachusetts, Worcester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 20 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in brain chemistry as measured by 1H-MRS scans (time frame: 14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2022.