Schizoaffective Disorder, Schizophrenia
Conditions
Brief summary
The investigators intend to explore the hypothesis that symptoms of schizophrenia may be reduced by the antimalarial compound artemisinin when used in addition to standard antipsychotic medications.
Detailed description
The aims of the current study are: 1. To evaluate the efficacy and side effects of artemisinin as an add-on compound for patients with schizophrenia who have residual psychotic symptoms of at least moderate severity. 2. To evaluate the effect of artemisinin on cognitive impairments and associated functional skills. 3. To investigate whether treatment with artemisinin produces a significant effect on the levels of antibodies to Toxoplasma. 4. To examine whether changes in cognitive impairment or psychiatric symptoms are correlated with changes in antibodies to Toxoplasma before and during the treatment with artemisinin.
Interventions
DIETARY_SUPPLEMENTArtemisinin
100 mg of artemisinin twice per day for 10 weeks
DIETARY_SUPPLEMENTIdentical looking placebo capsule
Identical looking placebo twice per day for 10 weeks
Sponsors
Stanley Medical Research Institute
Sheppard Pratt Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 years old. * Capacity for written informed consent. * Primary Axis I diagnosis (DSM-IV) of schizophrenia, any type, OR schizoaffective disorder (APA, 1994). * Currently an outpatient at the time of enrollment. * Residual psychotic symptoms which are at least moderately severe as evidenced by one or more Positive and Negative Syndrome Scale (PANSS) positive symptom scores, and/or PANSS negative symptom scores of 4 or more; OR a total PANSS score of 50 or more, containing at least three positive or negative items with scores of 3 or more at screening. * Conformance to Patient Outcome Research Team (PORT) Treatment Recommendation #5, Maintenance Antipsychotic Medication Dose (Lehman et al., 2004). * Receiving antipsychotic medication for at least 8 weeks prior to starting the study with no medication changes within the previous 21 days. * Participants must be proficient in English.
Exclusion criteria
* Diagnosis of mental retardation. * History of IV drug use. * Any serious medical condition that affects brain or cognitive functioning (e.g., epilepsy, serious head injury, brain tumor or other neurological disorder). * HIV infection or other immunodeficiency condition. * Primary diagnosis of substance abuse or dependence according to DSM-IV criteria within the last three months. * Participated in any investigational drug trial in the past 30 days. * Pregnancy or planning to become pregnant during the study period. * Any clinically significant or unstable medical disorder as determined by the investigators that would preclude study participation, including congestive heart failure, abnormal liver function or disease, renal failure, and any diagnosis of cancer undergoing active treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | 10 weeks (weeks 2 & 12) | The Positive and Negative Syndrome Scale (PANSS) measures psychiatric symptomatology, especially related to psychosis. The complete PANSS contains ratings for 30 symptoms, including 7 positive symptoms, 7 negative symptoms, and 16 general psychiatric symptoms. The severity of each symptom is rated on a scale ranging from 1 (minimal) to 7 (extreme); higher scores indicate increased symptomatology. Total PANSS scores include scores from all categories and range from 30 to 210 units on a scale. PANSS positive symptom scores and negative symptom scores each range from 7 to 49 units on a scale. |
Secondary
| Measure | Time frame |
|---|---|
| Change in Cognitive Functioning as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status and Change in Functional Performance as Measured by the UCSD Performance-based Skills Assessment. | 10 weeks (weeks 2 & 12) |
Countries
United States
Participant flow
Recruitment details
We enrolled n=66 participants drawn from the Sheppard Pratt Health System and from rehabilitation and treatment programs in Central Maryland. Dates of recruitment 8/08-1/10.
Pre-assignment details
We used a two week placebo run in for all participants
Participants by arm
| Arm | Count |
|---|---|
| Artemisinin Artemisinin 100 mg capsule Artemisinin (qinghaosu) is the antimalarial principle isolated by Chinese scientists from Artemisia annua L. (Sweet Wormwood plant), which has been in use in China for more than 2,000 years as an herbal tea against fever (van Agtmael et al., 1999). Artemisinin is a sesquiterpene trioxane lactone with a peroxide bridge linkage and is poorly soluble in oils or water. Johns Hopkins collaborators recently synthesized novel, nonacetal, hydrolytically stable derivatives of artemisinin and showed that they inhibit the replication of Toxoplasma gondii in cell culture (Jones-Brando et al., 2006). | 33 |
| Placebo Identical looking placebo capsule The placebo will contain an inert powder which is typically used to make many pharmaceutical tablets. The control capsules will be identical looking to the artemisinin capsules and will be prepared for use in this study by the Temple University Pharmacy which has experience in preparing materials for clinical trials. | 33 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other reason | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo | Artemisinin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants | 33 Participants | 66 Participants |
| Age Continuous | 49.2 years STANDARD_DEVIATION 9.2 | 45.4 years STANDARD_DEVIATION 9 | 47.3 years STANDARD_DEVIATION 9.3 |
| Region of Enrollment United States | 33 participants | 33 participants | 66 participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 28 Participants |
| Sex: Female, Male Male | 18 Participants | 20 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 31 |
| serious Total, serious adverse events | 3 / 33 | 3 / 33 |
Outcome results
Primary
Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12
The Positive and Negative Syndrome Scale (PANSS) measures psychiatric symptomatology, especially related to psychosis. The complete PANSS contains ratings for 30 symptoms, including 7 positive symptoms, 7 negative symptoms, and 16 general psychiatric symptoms. The severity of each symptom is rated on a scale ranging from 1 (minimal) to 7 (extreme); higher scores indicate increased symptomatology. Total PANSS scores include scores from all categories and range from 30 to 210 units on a scale. PANSS positive symptom scores and negative symptom scores each range from 7 to 49 units on a scale.
Time frame: 10 weeks (weeks 2 & 12)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Artemisinin | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 2 PANSS total symptom score | 64 units on a scale | Standard Deviation 8.74 |
| Artemisinin | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 12 PANSS positive score | 14.92 units on a scale | Standard Deviation 5.11 |
| Artemisinin | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 12 PANSS negative score | 18.69 units on a scale | Standard Deviation 3.69 |
| Artemisinin | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 2 PANSS negative score | 19.08 units on a scale | Standard Deviation 3.12 |
| Artemisinin | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 2 PANSS general score | 29.5 units on a scale | Standard Deviation 5.32 |
| Artemisinin | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 2 PANSS positive score | 15.42 units on a scale | Standard Deviation 4.18 |
| Artemisinin | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 12 PANSS general score | 27.81 units on a scale | Standard Deviation 4.78 |
| Artemisinin | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 12 PANSS total symptom score | 61.42 units on a scale | Standard Deviation 10.53 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 12 PANSS general score | 30.94 units on a scale | Standard Deviation 4.84 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 12 PANSS positive score | 16.35 units on a scale | Standard Deviation 5.35 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 2 PANSS total symptom score | 68.13 units on a scale | Standard Deviation 9.07 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 12 PANSS total symptom score | 66.32 units on a scale | Standard Deviation 9.45 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 2 PANSS positive score | 16.26 units on a scale | Standard Deviation 3.96 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 2 PANSS negative score | 19.77 units on a scale | Standard Deviation 3.48 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 12 PANSS negative score | 19.03 units on a scale | Standard Deviation 3.67 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Score From the Beginning to the End of the Double-blind Treatment Phase Weeks 2-12 | Week 2 PANSS general score | 32.10 units on a scale | Standard Deviation 6.18 |
Comparison: Repeated measures analaysis of variancep-value: >0.1ANOVA
Secondary
Change in Cognitive Functioning as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status and Change in Functional Performance as Measured by the UCSD Performance-based Skills Assessment.
Time frame: 10 weeks (weeks 2 & 12)