Clinical trial NCT00356200: Fluphenazine Decanoate for Psoriasis
Official title: Ascending-Dose, Double-Blind, Placebo-Controlled, Bilateral Study of Intralesional Fluphenazine Decanoate in Psoriasis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Psoriasis
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
Collaborators: name: Immune Control
First posted: 2006-07-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Target Lesion Score at Week 4 Compared to Baseline
timeFrame: Baseline to week 4
Secondary outcomes:
measure: Change in Target Lesion Pruritus Visual Analog Scale (VAS) at Week 4 Compared to Baseline.
timeFrame: Baseline to week 4
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts-New England Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center
name: Alice B Gottlieb, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tutrone WD, Kagen MH, Barbagallo J, Weinberg JM. Biologic therapy for psoriasis: a brief history, II. Cutis. 2001 Dec;68(6):367-72.
citation: Kipnis CD, Myers WA, Opeola M, Gottlieb AB. Biologic treatments for psoriasis. J Am Acad Dermatol. 2005 Apr;52(4):671-82. doi: 10.1016/j.jaad.2004.12.032. No abstract available.
citation: Gupta MA, Gupta AK. Psychiatric and psychological co-morbidity in patients with dermatologic disorders: epidemiology and management. Am J Clin Dermatol. 2003;4(12):833-42. doi: 10.2165/00128071-200304120-00003.
citation: Gupta MA, Guptat AK. The use of antidepressant drugs in dermatology. J Eur Acad Dermatol Venereol. 2001 Nov;15(6):512-8. doi: 10.1046/j.1468-3083.2001.00278.x.