Fluphenazine Decanoate for Psoriasis

Phase 2

Terminated

Conditions: Psoriasis

Interventions: Drug: Fluphenazine Decanoate
Drug: Placebo

Registration Number: NCT00356200

Lead Sponsor: Tufts Medical Center

Brief Summary: We are doing this research study to evaluate the effectiveness and safety of fluphenazine decanoate when injected with a needle into psoriasis lesions in adults. Fluphenazine decanoate is FDA (U.S. Food and Drug Administration) approved for use in people who have schizophrenia and psychotic symptoms. Fluphenazine decanoate is not approved by the FDA for use in psoriasis. Fluphenazine decanoate slows T cell growth in cells in laboratory test tubes. Its usefulness and safety in people with psoriasis will be investigated in this study.

Detailed Description: Psoriasis is a hyperproliferative, inflammatory, immune-mediated skin disease that affects approximately 2% of the United States and European populations (Tutrone 2001, Kipnis 2005). This disease manifests as red, scaly plaques that are itchy and/or painful. Patients with psoriasis may be socially stigmatized because of their appearance. Currently, there is no cure for this condition. Often, repeated medical treatments are necessary and can become expensive. Treatment with topical corticosteroids is the mainstay therapy for mild to moderate psoriasis. In more severe cases, systemic therapies (e.g., cyclosporine) and phototherapy (e.g., ultraviolet B (UVB) irradiation) are used. These treatments, however, are associated with toxicities or inconvenience. There is anecdotal evidence to suggest that antipsychotic drugs have a beneficial effect on psoriasis (Gupta 2001, 2003).

Fluphenazine is a phenothiazine antipsychotic drug. In vitro, fluphenazine kills activated human T cells under conditions that do not affect resting T cells (Immune Control Inc. data not shown). To determine the size of a therapeutic window for human peripheral blood mononuclear cells (PBMC)s, Immune Control Inc. performed the following experiments. First, phytohemagglutinin- (PHA)-activated cells were exposed to 2, 10, or 20 µM fluphenazine for 0, 18, 24, 36, 48, or 72 hours. Second, resting cells were exposed to identical fluphenazine concentrations for identical time periods, after which the drug was washed out of the cells, and the cells activated with PHA. In all cases, deoxyribonucleic acid (DNA) synthesis was measured by exposing the cells to tritiated thymidine, and measuring the incorporated nucleotide by scintillation counting. The data show that exposure of activated cells to 10 µM fluphenazine for 72 hours, or 20 µM fluphenazine for 36 hours, caused the death of virtually all of the activated cells. The ability of the resting cells to initiate DNA synthesis after activation, by contrast, was largely unaffected by these fluphenazine exposures. Although we cannot precisely control intralesional fluphenazine concentrations, we expect that injections of up to 1 mg fluphenazine decanoate will yield local concentrations that exceed 10 µM without significant systemic fluphenazine concentrations.

We propose that fluphenazine will suppress proliferating T-lymphocytes in psoriatic plaques in vivo and thus result in healing of plaques. The objective of this study is to assess the safety and biologic activity of intralesional injection of fluphenazine decanoate in adult subjects with psoriasis.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Adults 18 to 65 years of age with psoriasis, in general good health
Must have symmetric target lesions approximately 2-4 cm in diameter on each side of the body (e.g., thighs) with baseline target lesion score of 6 or higher (scale of 0-12) for each target
Women of childbearing potential must agree to use two forms of contraception for the duration of the study

Exclusion Criteria

Infliximab (Remicade) or alefacept (Amevive) within the past 6 months (24 weeks)
Etanercept (Enbrel), efalizumab (Raptiva), adalimumab (Humira), or other tumor necrosis factor- (TNF)-alpha inhibitor within the past 3 months (12 weeks)
Other systemic psoriasis therapies (e.g., methotrexate, cyclosporine, acitretin) or PUVA (psoralen plus ultraviolet A) within the past 4 weeks
Ultraviolet B (UVB) or topical therapy (other than over the counter (OTC) moisturizers and shampoos) within the past 2 weeks (including topical corticosteroids, vitamin A and D analogues)
Receipt of an investigational agent within the past 4 weeks
Systemic corticosteroid therapy
Inability to understand consent or comply with protocol
Pregnancy, lactation, or unwillingness to use adequate birth control during the study
Impaired hepatic function
Known Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis B/C
Blood dyscrasia
Epilepsy
Tardive dyskinesia
Excessive alcohol consumption
Current use of selective serotonin reuptake inhibitors (SSRI), tricyclic, or norephinephrine reuptake inhibitor antidepressants or use within 6 weeks of beginning the study
Concurrent use of anti-seizure drugs, with the exception of gabapentin for treatment of neuropathy
Use of phenothiazine antipsychotics or anticholinergics
Known allergy to fluphenazine decanoate or other phenothiazines
Known allergy to parabens/para-aminobenzoic acid (PABA), benzyl alcohol, sesame oil or sesame seeds
Clinically significant mitral valve disease
Clinically significant and uncontrolled cardiovascular disease
QTc >450 msec, or evidence of a clinically significant dysrhythmia on electrocardiography (ECG)
Operator of heavy machinery
Pheochromocytoma
History of breast cancer
History of seizure disorder
Occupational exposure to organophosphate insecticides
Parkinson's disease and other related movement disorders
Lab abnormalities including:
Alanine aminotranferease (ALT)/aspartate aminotransferase (AST) ≥ 2X upper limit of reference range
Creatinine ≥ 1.5X upper limit of reference range
Bilirubin ≥ 2X upper limit of reference range
Absolute total lymphocyte or polymorphonuclear leucocyte count ≤ 1000/uL or ≥ 3X upper limit of ref range
Platelets ≤ 80,000/uL
Hemoglobin ≤ 8.0 g/dL
Glucose ≥ 200 mg/dL
Fasting blood sugar ≥ 126 mg/dL
Concurrent use of drugs listed in Appendix F

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluphenazine treated	Fluphenazine Decanoate	Treated with fluphenazine
Placebo	Placebo	Treated with Placebo

Primary Outcome Measures

Name	Time	Method
Change in Target Lesion Score at Week 4 Compared to Baseline	Baseline to week 4	Change in score from 0-14 of target lesion disease activity based on scaling, erythema, and induration as determined by a physician assessor at week 4 compared to baseline (with 0 being no disease activity and 14 being maximum disease activity).

Secondary Outcome Measures

Name	Time	Method
Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline.	Baseline to week 4	Target lesion pruritus as measured by the Visual Analog Scale (VAS) from 0 to 100 mm at week 4 compared to baseline (with 0 being no pruritis and 100 being maximum pruritis).