SchizophreniaNCT02118610
Treatment of Schizophrenia With L-tetrahydropalmatine (l-THP): a Novel Dopamine Antagonist With Anti-inflammatory and Antiprotozoal Activity
A study testing L-tetrahydropalmatine (30mg) and Sugar pill in people with Schizophrenia, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
Schizophrenia is a devastating and complex illness, with multiple symptom and behavioral manifestations. Antipsychotic medications are the mainstay of treatment; however, many patients only partially respond to treatment. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- L-tetrahydropalmatine (30mg) and Sugar pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Jun 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder
- Minimum score of 45 on the total Brief Psychiatric Rating scale or a CGI of 4
- Age 18-64 years
- Currently taking antipsychotic regimen with no dose changes in last 30 days
- Ability to consent determined by a score of 10 or greater on the Evaluation to Sign Consent
Who cannot join
- Women who are pregnant, nursing, or not using effective contraception (if capable of getting pregnant)
- Current organic brain disorder or mental retardation
- Medical condition whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with study medication. This includes HIV, kidney disease, congestive heart failure, pheochromocytoma, untreated hyperthyroidism, dehydration, fever, uncorrected congenital heart defect, seizures, electrolyte imbalance, uncontrolled diabetes mellitus, porphyria variegate, superventricular tachycardia, atrial fibrillation, cardiomyopathy, or cancer. This also may include other medical conditions where the medically accountable investigator in the study does not think it would be in the best interest of the participant to participate in the study.
- Current (past month) substance abuse or dependence (DSM-IV criteria) other than nicotine or caffeine; substance use, per se, will not be exclusionary
- Inability to provide valid informed consent
- Inability to understand English
- Inability to cooperate with study procedures
- Taking herbal or homeopathic medications where the metabolism of the drug is not known
Trial locations and contacts
1 site in 1 country.
United States1 site
Maryland Psyciatric Research Center
Catonsville, Maryland, 21228
About this study
Schizophrenia is a devastating and complex illness, with multiple symptom and behavioral manifestations. Antipsychotic medications are the mainstay of treatment; however, many patients only partially respond to treatment. Development of new treatment has not progressed rapidly, in part, because the underlying etiopathophysiology of the illness is not well understood. To date, all pharmacological treatments approved for use in schizophrenia involve primary modulation of the dopamine system. Many agents without dopamine action have failed to demonstrate efficacy. There is growing evidence that schizophrenia may be, in part, due to an inflammatory process and pharmacological treatment approaches that decrease inflammation have shown promise. Thus, treatments that may have anti-inflammatory properties (e.g., TNF-alpha inhibition), but also possess dopamine modulation may prove to be beneficial. This novel medication, l-tetrahydropalmatine (l-THP), has robust anti-inflammatory properties, particularly TNF-alpha and ICAM inhibition; has antiprotozoal activity; and possesses an antipsychotic-like pharmacological profile of D1, D2 and D3 receptor antagonism. The high affinity of l-THP for D1 versus D2 receptors distinguishes it from first generation antipsychotics and its D1 to D2 ratio resembles that of the superior antipsychotic, clozapine. Also, an almost identical compound, l-stepholindine (l-SPD), demonstrates robust antipsychotic activity in humans (both positive and negative symptoms) and is currently used clinically in China. l-THP has been used for over 40 years clinically in China, has a good safety profile to date, and represents a novel and exciting mechanism for schizophrenia treatment. Initial safety data from our phase I study of l-THP (20 healthy controls) shows excellent tolerability and lack of any substantial side effects. L-THP has been tested in outpatient drug abuse trials for 4 weeks with good safety data, (Hu et al 2006, Yang et al 2003). Yang et al (2003) randomized this medication in over 120 participants for 4 weeks with 4 week observation without any notable side effects.
We will test this compound (30 mg BID) as an adjunct treatment in a randomized, double-blind, 4-week trial, in which we will assess treatment efficacy, changes in peripheral cytokine concentrations, and, secondarily, antiprotozoal effects, (antibody titers to Toxoplasma gondii), an infection that is known to occur at higher rates in schizophrenia than healthy controls and may be related in part to the illness.
- Conditions
- Schizophrenia
- Being tested
- L-tetrahydropalmatine (30mg), Sugar pill
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-tetrahydropalmatine (30mg)Drug
Active comparator
Sugar pillDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| l-tetrahydropalmatine | Experimental | l-tetrahydropalmatine (30 mg BID) Receives: Drug: L-tetrahydropalmatine (30mg) |
| Sugar Pill | Placebo comparator | Not described Receives: Drug: Sugar pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive and Negative Symptom Improvement
Measured by the Brief Psychiatric Rating Scale, positive symptom subfactor, Scale for the Assessment of Negative Symptoms (SANS) and Brief Negative Symptom Scale (BNSS).
The total BPRS score is calculated by adding the scores for scales #1-#18. Each scale ranges from "1=Not Present" to "7=Very Severe". Total scores range from a minimum score of 18 to a maximum score of 126. A higher total score indicates a more severe psychiatric symptom rating.
Measured: Baseline and 4 weeks (endpoint)
Secondary outcomes (1)
Improvement in Cognitive Function
Neuropsychological testing will be done at baseline and endpoint using the MATRICS battery. A composite score as well as individual scores will be will be the outcome. This assessment total minimum score of -10 and maximum score of 80. The higher the score the better the outcome.
Measured: Baseline and 4 weeks (endpoint)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study startSep 2014
- Primary completionDec 2018
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Responsible party
- Principal investigator, Deanna Kelly, University of Maryland, Baltimore
- Investigators
- Deanna L Kelly, Parm.D., BCPP, Principal investigator, University of Maryalnd, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02118610
- Sponsor's protocol ID
- HP-00058491
- Status last verified
- Jan 2022
- First submitted
- 14 Apr 2014
- Last updated
- 6 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Schizophrenia With L-tetrahydropalmatine (l-THP): a Novel Dopamine Antagonist With Anti-inflammatory and Antiprotozoal Activity
- ClinicalTrials.gov ID
- NCT02118610
- Acronym / sponsor ID
- HP-00058491
- Conditions
- Schizophrenia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- Sep 2014
- Primary completion
- Dec 2018 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Posted 7 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Schizophrenia is a devastating and complex illness, with multiple symptom and behavioral manifestations. Antipsychotic medications are the mainstay of treatment; however, many patients only partially respond to treatment. Development of new treatment has not progressed rapidly, in part, because the underlying etiopathophysiology of the illness is not well understood. To date, all pharmacological treatments approved for use in schizophrenia involve primary modulation of the dopamine system. Many agents without dopamine action have failed to demonstrate efficacy. There is growing evidence that schizophrenia may be, in part, due to an inflammatory process and pharmacological treatment approaches that decrease inflammation have shown promise. Thus, treatments that may have anti-inflammatory properties (e.g., TNF-alpha inhibition), but also possess dopamine modulation may prove to be beneficial. This novel medication, l-tetrahydropalmatine (l-THP), has robust anti-inflammatory properties, particularly TNF-alpha and ICAM inhibition; has antiprotozoal activity; and possesses an antipsychotic-like pharmacological profile of D1, D2 and D3 receptor antagonism. The high affinity of l-THP for D1 versus D2 receptors distinguishes it from first generation antipsychotics and its D1 to D2 ratio resembles that of the superior antipsychotic, clozapine. Also, an almost identical compound, l-stepholindine (l-SPD), demonstrates robust antipsychotic activity in humans (both positive and negative symptoms) and is currently used clinically in China. l-THP has been used for over 40 years clinically in China, has a good safety profile to date, and represents a novel and exciting mechanism for schizophrenia treatment. Initial safety data from our phase I study of l-THP (20 healthy controls) shows excellent tolerability and lack of any substantial side effects. L-THP has been tested in outpatient drug abuse trials for 4 weeks with good safety data, (Hu et al 2006, Yang et al 2003). Yang et al (2003) randomized this medication in over 120 participants for 4 weeks with 4 week observation without any notable side effects.
We will test this compound (30 mg BID) as an adjunct treatment in a randomized, double-blind, 4-week trial, in which we will assess treatment efficacy, changes in peripheral cytokine concentrations, and, secondarily, antiprotozoal effects, (antibody titers to Toxoplasma gondii), an infection that is known to occur at higher rates in schizophrenia than healthy controls and may be related in part to the illness.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| l-tetrahydropalmatine | Experimental | Drug: L-tetrahydropalmatine (30mg)l-tetrahydropalmatine (30 mg BID) |
| Sugar Pill | Placebo comparator | Drug: Sugar pill |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder
- Minimum score of 45 on the total Brief Psychiatric Rating scale or a CGI of 4
- Age 18-64 years
- Currently taking antipsychotic regimen with no dose changes in last 30 days
- Ability to consent determined by a score of 10 or greater on the Evaluation to Sign Consent
Key exclusion criteria (8 listed)
- Women who are pregnant, nursing, or not using effective contraception (if capable of getting pregnant)
- Current organic brain disorder or mental retardation
- Medical condition whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with study medication. This includes HIV, kidney disease, congestive heart failure, pheochromocytoma, untreated hyperthyroidism, dehydration, fever, uncorrected congenital heart defect, seizures, electrolyte imbalance, uncontrolled diabetes mellitus, porphyria variegate, superventricular tachycardia, atrial fibrillation, cardiomyopathy, or cancer. This also may include other medical conditions where the medically accountable investigator in the study does not think it would be in the best interest of the participant to participate in the study.
- Current (past month) substance abuse or dependence (DSM-IV criteria) other than nicotine or caffeine; substance use, per se, will not be exclusionary
- Inability to provide valid informed consent
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-tetrahydropalmatine (30mg)Active comparator | Drug | l-tetrahydropalmatine |
| Sugar pillPlacebo | Drug | Sugar Pill |
Primary outcome
Positive and Negative Symptom Improvement
Time frame: Baseline and 4 weeks (endpoint)
Measured by the Brief Psychiatric Rating Scale, positive symptom subfactor, Scale for the Assessment of Negative Symptoms (SANS) and Brief Negative Symptom Scale (BNSS). The total BPRS score is calculated by adding the scores for scales #1-#18. Each scale ranges from "1=Not Present" to "7=Very Severe". Total scores range from a minimum score of 18 to a maximum score of 126. A higher total score indicates a more severe psychiatric symptom rating.
1 secondary outcome
Improvement in Cognitive Function
Time frame: Baseline and 4 weeks (endpoint)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Maryland Psychiatric Research CenterLink provided by the sponsor.
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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.
Deanna L Kelly, Parm.D., BCPP principal investigator
University of Maryalnd, Baltimore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-tetrahydropalmatine (30mg) and Sugar pill in people with Schizophrenia, run by University of Maryland, Baltimore 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 5 inclusion and 8 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: finished, as of the sponsor's last update on 6 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Positive and Negative Symptom Improvement (time frame: Baseline and 4 weeks (endpoint)). 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 6 Jan 2022.