Acitretin

1. BIOENGINEERED SKIN AND WOUND HEALING

This study is currently recruiting patients.

Sponsored by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

This study will look at whether a graft of bioengineered skin (BSC), known commercially as Apligraf, stimulates the healing process in a person's own skin at the edge of a wound (known as the edge effect). The information from this study will provide a better understanding of the ways that grafts of bioengineered skin help the healing of chronic wounds.

We will assign study participants to either the bioengineered skin group or the control group. People in the control group will receive compression therapy with a multilayered compression bandage. We will examine each participant before starting treatment and then once a week for 24 weeks or until the wound heals. On the first day of treatment (day 0) and at week 3, week 6, and week 24 (end of treatment) we will take a small tissue sample from the wound for a biopsy. After the wound is completely healed, we will ask the patient to return once a month for 6 months to make sure the wound stays healed.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Active Control, Single Group Assignment, Safety/Efficacy Study

Official Title: Mechanisms of Bioengineered Skin in Human Wounds

Further Study Details:

BSC is a two-layered sheet made from purified beef tendon collagen, living human cells, and a substance that maintains the cells until they are grafted (removed). We will obtain human cells from donors unrelated to the patient. The human cells have been tested for the presence of infectious agents and found to be free of disease-causing organisms such as hepatitis virus, the AIDS virus, bacteria, and fungi.

We will randomly assign (randomize) study participants to either the bioengineered skin group or control group (compression therapy with a multilayered compression bandage). Regardless of the group to which a patient is assigned, we expect participation in this study for 12 months following the start of study treatment. We will examine each patient at the screening visit (2 weeks before randomization) and then again 3-4 days before the start of treatment to make sure the wound is free of any signs of infection. After the initial randomization visit we will examine the wound once a week for 24 weeks or until the wound heals, whichever is earlier. As soon as we have determined that the wound is completely healed, we will ask the patient to return once a month for 6 months to make sure it remains healed.

Bioengineered skin group: We will apply BSC to the wound and cover it with xeroform dressing, foam bolster, gauze dressing, and compression bandage. If we do not note any improvement at the week 6 visit, we will apply BSC on the wound a second time.

Control group: We will place a multilayered compression bandage on the wound of participants assigned to this group.

Biopsies (small piece of skin tissue): At day 0 a biopsy will be taken from the thigh and leg ulcer. The biopsy from the thigh will require sutures and will be removed in ten days. Sometime between weeks 1 and 3, and at the week 6, week 24, and week 48 (6 month follow-up) visits a biopsy will be taken from the ulcer (wound) if the ulcer has not healed. If the ulcer is healed at the week 48 visit, a light scraping of the healed wound will be performed.

Study examinations: All study examinations will include observation, measurement, and photography.

We can only admit women of childbearing age to the study if they are not breast feeding, not pregnant, or have been surgically sterilized or are using effective birth control. Because the effects of the proposed treatments on a fetus are unknown, we will remove from the study any woman who becomes pregnant while receiving BSC applications (day 0-week 3) and suggest another method of treatment.

2. STUDY OF MYCOBACTERIAL INFECTIONS

This study is currently recruiting patients.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

This study will examine the symptoms, course of disease and treatment of non-tuberculous mycobacterial (NTM) infections, as well as the genetics involved in these infections. Patients with NTM have recurrent lung infections and sometimes infections of the skin and other organs as well. They may also have curvature of the spine, barrel chest, and heart valve weakness. The study will compare the features of NTM with those of Job syndrome and cystic fibrosis, other diseases involving recurrent infections of the lungs and possibly other organs. Patients with diagnosed or suspected non-tuberculous mycobacterial infection, cystic fibrosis, or Job syndrome may be eligible for this study. All participants will have a medical and family history, blood and urine tests, imaging studies that may include X-rays, computed tomography (CT) or magnetic resonance imaging (MRI) scans, and DNA and other genetic studies. In addition, all patients with Job syndrome and cystic fibrosis, and patients with NTM who have lung disease undergo the following procedures:

* Scoliosis survey

* X-rays of the spine to look for curvature or other abnormalities of the spinal column

* Echocardiography

* Imaging test that uses sound waves to examine the heart chambers and valves

* Electrocardiogram

* Measurement of the electrical activity of the heart

* Pulmonary function tests

* Breathing tests to measure how much air the patient can move into and out of the lungs

* Body measurements

* Measurements of height, weight, arm span, finger length, etc.

* Joint function

* Assessment of joint mobility using different maneuvers to test flexibility of joints and ligaments

* Examination of physical features that might be associated with NTM, such as high arched palate of the mouth, flat feet, or certain skin features

* Dermatology (skin) examination for reactive skin conditions or other skin problems and possibly a skin biopsy (surgical removal of a small skin tissue sample for microscopic examination)

* Interview with genetics specialist.

These tests may require several days to complete. Patients with NTM will also be examined by a cystic fibrosis specialist and may have a sweat test. In addition, NTM patients will be asked to return to NIH every year for 5 years for follow-up tests, if medically indicated, including CT of the chest, scoliosis survey, and examination by other specialists.

CONDITION

Atypical Mycobacterium Infections Cystic Fibrosis Job's Syndrome

Study Type: Observational

Study Design: Natural History

Official Title: Natural History, Genetics, Phenotype, and Treatment of Mycobacterial Infection

Further Study Details:

The nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms found in soil and water that rarely cause disease in humans. Since exposure to these organisms is universal and disease is rare, it can be concluded that normal host defenses are sufficient to prevent infection. It follows that otherwise healthy individuals that develop disease may have abnormal susceptibility or immune defects that permit infection with nontuberculous mycobacteria. The organisms that are most commonly encountered in clinical practice include Mycobacterium avium, and M. intracellulare [collectively known as the M. avium complex (MAC)], M. kansasii, M. fortuitum, M. abscessus, and M. chelonae. These organisms share significant structural and biochemical similarities with their more pathogenic relative, M. tuberculosis (MTB). Recognition of host factors that predispose or lead to NTM infection may have important implications for pathogenesis and therapeutic intervention, and may be applicable to the more virulent MTB. Identification of genetic or acquired susceptibility factors may lead to recognition of endogenous pathways that can be exploited therapeutically and to possible gene identification. Over the last two decades, three important observations have been made regarding the pathogenesis of nontuberculous mycobacterial infections. 1) In patients infected with HIV, nontuberculous mycobacterial infections often occur when the CD4+ T-lymphocyte number falls below 50/mm(3). This suggested that specific T cell products or activities were required for mycobacterial resistance. 2) An association was noted between pulmonary nontuberculous mycobacterial infections and a particular body habitus, predominantly in post-menopausal women (pectus excavatum, scoliosis, mitral valve prolapse). 3) Multiple defects have been found involving the interferon gamma synthesis and use pathways in patients with disseminated nontuberculous mycobacterial infection without HIV, suggesting this is a critical pathway for host defense against these organisms. We seek to better characterize the predisposition to mycobacterial infection. This study will specifically address several aspects of immune function and investigate the proposed link to body morphotype in the relevant population. Including patients with mycobacterial infections currently followed on other protocols who will enroll in this protocol, we anticipate 250 patients over 5 years. By collecting this information, we hope to provide insight into disease associations, infection susceptibility, and genetic predisposition to mycobacterial infection.

3. HEALTH SERVICES IMPLICATIONS OF A TELEDERMATOLOGY CONSULT SYSTEM

This study is currently recruiting patients.

Sponsored by: Department of Veterans Affairs

Department of Veterans Affairs Health Services Research and Development Service

We have previously shown (IIR 95-045) that teledermatology, using store and forward technology, can result in reliable and accurate diagnostic outcomes when compared to clinic-based dermatology consultations. This current investigation builds on that fundamental diagnostic information to assess the health services implications of a teledermatology consult system. A systematic evaluation of teledermatology that includes assessments of resource utilization, an economic analysis, and patient and physician satisfaction are important when considering implementation of telemedicine for dermatologic health care delivery. Building on our findings showing comparable diagnostic accuracy and reliability, our objective is to further explore the health services issues related to teledermatology. Outcomes of interest are the time to diagnosis and treatment initiation, number of patients requiring a clinic-based encounter, time studies for each consult modality, descriptive measures of patient and clinician satisfaction, and an economic analysis. This is a randomized clinical trial comparing teledermatology consultations with usual care dermatology clinic consultations. Patients referred from primary care clinics to the dermatology consult service are randomized either to usual care, typically the next available appointment, or a teledermatology consultation. A teledermatology consultation consists of a digital image(s) and a standardized history. The consultant dermatologist, upon review of the teledermatology consultation, decides on the need for a clinic-based evaluation. Patients may be scheduled for a clinic visit or, alternatively, the consultant dermatologist may provide recommendations for the referring clinician to implement. Outcome measures are collected and recorded through longitudinal follow-up.

Study Type: Interventional

Study Design: Diagnostic, Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study

4. SCREENING HERBS FOR DRUG INTERACTIONS

This study is currently recruiting patients.

Sponsored by: National Center for Complementary and Alternative Medicine (NCCAM)

The present study is designed to detect potential herb-drug interactions in human volunteers. Research subjects, who have had physicals and found to be healthy, and, who are taking no medications or supplements, will receive a single dose of the prescription drug alprazolam and the over-the-counter cough suppressant, dextromethorphan on two occasions: once by themselves, and again after taking a selected herbal product for 2 weeks. Comparisons will be made between the blood and urine levels of alprazolam and dextromethorphan, respectively, between the two treatment phases. This information will allow us to make predictions on potential herb-drug interactions with many prescription medications.

Study Type: Interventional

Study Design: Prevention, Non-Randomized, Open Label, Active Control, Single Group Assignment, Pharmacokinetics Study

Official Title: R-21 Project: Screening Herbs for Drug Interference

Further Study Details:

The use of herbal agents by the lay public and medical professionals has accelerated in the last decade. Additionally, there has been increasing interest by the NIH National Center for Complementary & Alternative Medicine (NCCAM) and others in the safety and efficacy of herbal medicines in the treatment of a variety of medical and psychiatric conditions. It has also become evident that herbal medications are being used concomitantly with conventional prescription and over-the-counter medications. However, the systematic evaluation of the potential of these agents to interact with conventional medications has been generally neglected. Compounding this problem is the fact that even single entity herbal products can contain a multitude of naturally occurring chemicals which serve as candidates for potential herb-drug interactions by inhibiting or inducing specific hepatic isozymes. Numerous reports document the importance of pharmacokinetic interactions involving inhibition or induction of the cytochrome P450 (CYP) enzyme system. Importantly, recent publications have documented that clinically significant herb-drug interactions can occur. Prominent examples include herb-induced reductions in plasma concentrations of the anti-HIV medication indinavir and the immunosuppressant cyclosporine by St. John's wort (Hypericum perforatum). In vitro screening studies are of limited value due to difficulties in approximating physiologic concentrations, assessing the influence of non-hepatic metabolism, and accounting for the contribution of active metabolites. However, based upon findings of the effects of concurrently administered herbs on the metabolism of enzyme specific probe drug substrates alprazolam (CYP 3A4) and dextromethorphan (CYP 2D6), the potential specificity and magnitude of CYP enzyme inhibition and/or induction can be determined in normal volunteers. In a preliminary study in human subjects using this validated probe drug technique assessing inhibitory effects only, the investigators found no effects of St. John's wort on CYP 3A4 or CYP 2D6. In the present proposal, the 10 most commonly used herbal products in the US will be systematically evaluated for inhibition of CYP 3A4 and 2136, and induction of CYP 3A4. Collectively, these enzyme systems are involved in the metabolism of approximately 80% of all marketed medications. A combination of probe drugs will be given to normal volunteers both in the absence and presence of herbal medications. The plasma and urine concentration of these agents and their respective metabolites will be determined in order to evaluate individual herbal products degree and specificity of enzyme inhibitory or inductive effects. This data will fill a void regarding the relative safety of combining specific herbal agents with conventional medications and will serve as the basis for further investigations of other isozymes and herb interactions. Further, the proposed studies will complement existing and future NCCAM studies of agents such as St. John's wort and Gingko biloba.

5. ACITRETIN IN PREVENTING SKIN CANCERS IN PATIENTS WITH PREVIOUSLY TREATED SKIN CANCERS WHO HAVE UNDERGONE ORGAN TRANSPLANTATION

This study is currently recruiting patients.

Sponsored by: National Cancer Institute (NCI), North Central Cancer Treatment Group

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of acitretin may be an effective way to prevent the recurrence or further development of skin cancer.

PURPOSE: Randomized clinical trial to study the effectiveness of acitretin in preventing skin cancers in patients with at least two previously treated skin cancers who have undergone organ transplantation.

Study Type: Prevention

Official Title: Randomized Study of Acitretin in Patients with Multiple Prior Skin Cancers Who Received Solid Organ Transplantation

Further Study Details:

I. Determine the chemopreventive efficacy of acitretin in immunosuppressed solid organ transplant recipients with a history of multiple previous basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) skin cancer resections.

II. Evaluate human papillomavirus (HPV) as a possible etiologic cofactor in the development of cutaneous epidermal dysplasia/carcinoma from skin tissues of these patients.

III. Determine the effect of acitretin on potential surrogate endpoint biomarkers and HPV DNA in normal (sun protected), sunexposed, and dysplastic, and carcinoma (SCC/BCC) skin specimens.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified according to age (at least 18 to under 50 vs. 50 to 59 vs. 60 to 69 vs. 70 and over), number of prior skin cancers in past 5 years (2 vs. 3 vs. at least 4), time since most recent skin cancer occurrence (less than 12 months vs. at least 12 months), sunburn susceptibility (none vs. moderate vs. high), and visible skin damage (mild vs. moderate vs. severe).

Patients receive either oral acitretin or placebo daily for 2 years. Skin biopsies are obtained at 1 year from normal areas and from any areas with skin cancer for genetic studies.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 110 patients will be accrued for this study within 4-5 years.

6. CELECOXIB IN PREVENTING SKIN CANCER

This study is currently recruiting patients.

Sponsored by: National Cancer Institute (NCI)

RATIONALE: Celecoxib may be effective in preventing skin cancer by decreasing redness caused by exposure to ultraviolet light and changing potential skin cancer biomarkers. It is not yet known whether celecoxib is more effective than a placebo in preventing skin cancer.

PURPOSE: Randomized phase II trial to study the effectiveness of celecoxib in preventing skin cancer in participants exposed to ultraviolet light.

Study Type: Prevention

Official Title: Phase II Randomized Study of Celecoxib as a Chemopreventive Agent Inhibiting UV-Induced Erythema and Biomarkers of Cutaneous Carcinogenesis in Participants With Fitzpatrick Type I-IV Skin

Further Study Details:

I. Determine whether celecoxib decreases ultraviolet(UV)-induced erythema and affects surrogate biomarkers of potential neoplastic change in participants with Fitzpatrick type I-IV skin exposed to UV light.

PROTOCOL OUTLINE: This is a randomized, double-blind, placebo-controlled study. Participants are randomized to one of two treatment arms.

Arm l: Participants receive oral celecoxib twice daily for approximately 120 days.

Arm II: Participants receive oral placebo twice daily for approximately 120 days. Skin biopsies of UV-exposed sites are evaluated. Participants are followed for 1 month post-treatment.

PROJECTED ACCRUAL: A total of 36 participants (18 per arm) will be accrued for this study within 8 months.

7. PHOTODYNAMIC THERAPY IN TREATING PATIENTS WITH BASAL CELL SKIN CANCER

This study is currently recruiting patients.

Sponsored by: National Cancer Institute (NCI)

RATIONALE: Photodynamic therapy uses light and drugs that make cancer cells more sensitive to light to kill tumor cells. Photosensitizing drugs such as HPPH are absorbed by cancer cells and, when exposed to light, become active and kill the cancer cells.

PURPOSE: Phase I trial to study the effectiveness of photodynamic therapy with HPPH in treating patients who have basal cell skin cancer.

Study Type: Treatment

Official Title: Phase I Study of Photodynamic Therapy Using HPPH in Patients with Basal Cell Skin Cancer

Further Study Details:

I. Determine the safety of HPPH used in photodynamic therapy in patients with basal cell skin cancer.

II. Determine the drug dose, light dose, and treatment interval combinations that do not produce excessive toxicity to normal skin but effect tumor response in these patients treated with this regimen.

III. Determine the length of time for cutaneous photosensitivity in these patients treated with this regimen.

IV. Determine the plasma clearance rates for HPPH in these patients.

V. Determine the best combination of treatment parameters for a phase II study.

PROTOCOL OUTLINE: This is a dose-escalation study.

Patients receive HPPH IV on day 1. Patients undergo phototherapy on days 2-3.

Cohorts of 2-6 patients receive escalating doses of HPPH and phototherapy to determine the minimum erythemal dose (MED). The MED is defined as the dose combination of HPPH and laser light preceding that at which at least 1 patient experiences grade 3 or worse toxicity or at which at least 2 patients experience grade 1 or worse toxicity.

Patients are followed daily for 4 days, at week 1, and at months 1, 3, 6, 12, and 24.

PROJECTED ACCRUAL: A total of 4-25 patients will be accrued for this study.

8. INTERLEUKIN-12 GENE THERAPY IN TREATING PATIENTS WITH SKIN METASTASES

This study is currently recruiting patients.

Sponsored by: National Cancer Institute (NCI)

RATIONALE: Inserting the gene for interleukin-12 into a person's skin tumor cells may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I trial to study the effectiveness of interleukin-12 gene therapy in treating patients who have skin metastases.

Study Type: Treatment

Official Title: Phase I Study of Interleukin-12 Gene in Patients with Spontaneous Skin Metastases

Further Study Details:

I. Determine the safety and toxicity of interleukin-12 gene in patients with spontaneous skin metastases.

II. Determine the antitumor immune response in patients treated with this regimen.

III. Compare the toxicity of this regimen administered for 1 week vs. 2 weeks in these patients.

IV. Compare the local and systemic antitumor response in patients treated with this regimen administered for 1 week vs. 2 weeks.

PROTOCOL OUTLINE: Patients are stratified according to number of tumor sites (1 vs. 2 vs. 3 or more). Patients are assigned to 1 of 2 treatment arms.

Group A: Patients receive interleukin-12 gene intratumorally over 5 minutes on days 1, 3, and 5.

Group B: Patients receive IL-12 gene intratumorally over 5 minutes on days l, 3, 5, 8, 10, and 12. Patients with stable or responding disease may receive 1 subsequent course beginning on day 29. Patients are followed at 3, 6, and 12 months.

PROJECTED ACCRUAL: A total of 12 patients (6 per treatment group) will be accrued for this study.

9. INFLIXIMAB (REMICADE[R]) TO TREAT DERMATOMYOSITIS AND POLYMYOSITIS

This study is currently recruiting patients.

Sponsored by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

This study will examine whether infliximab (Remicade[R]) is safe and effective for the treatment of dermatomyositis and polymositis. Infliximab blocks the effect of a protein called tumor necrosis factor (TNF), which is associated with harmful inflammation in many diseases. Patients 18 years of age and older with active dermatomyositis or polymositis that does not respond adequately to treatment with methotrexate and corticosteroids may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests, chest x-ray, pulmonary function test, skin test for tuberculosis, HIV test, electromyography (described below), manual muscle testing, and functional assessments. Magnetic resonance imaging (described below) will be done to assess the degree and location of inflammation in the involved limbs. An electrocardiogram and echocardiogram will be done if recent ones are not available. Patients who qualify for the study will be asked to undergo two muscle biopsies (surgical removal and analysis of small pieces of muscle tissue), one before initiation of treatment, and another on the 16th week. Participants will be randomly assigned to receive either 3 mg/kg body weight of infliximab or a placebo (inactive substance) by infusion through a vein over 2 hours. The infusions will be given at the beginning of the treatment period (week 0) and at weeks 2, 6 and 14. At week 16, strength will be assessed by manual muscle testing. Patients who improved with treatment will continue with the same infusion dose on week 18, 22, 30, and 38. Those who do not improve will be assigned by random allocation to receive either 5 mg/kg body weight or l0/mg/kg body weight of infliximab on weeks 18, 22, 30, and 38. Those who did not improve who were previously on the placebo infusion will receive an extra dose of either 5 mg/kg or 10 mg/kg body weight of infliximab on week 16, while those patients who were previously on 3 mg/kg body weight of infliximab who failed to meet the improvement criteria will receive an infusion containing no medication on week 16. Patients will be admitted to the hospital for infusions at weeks 0, 14, and 38; the rest will be given on an outpatient basis. After the 38th week, all infusions will be stopped and patients will be assessed on the 40th week. Participants will undergo some or all of the following tests and evaluations during treatment:

* Blood tests every week to look for antibodies seen with muscle inflammation. Some of the blood samples will be stored for later testing, including genetic studies to find genetic differences related to inflammation.

* Skin test for tuberculosis

* Chest x-rays at the beginning of the study (if a recent one is not available) and again at weeks 16 and 40 to look for active infection, detect signs of past exposure or infection with diseases such as tuberculosis, and assess the presence of lung disease that might be related to the myositis.

* MRI (usually of the legs) at the beginning of the study and again at weeks 16 and 40 to measure disease activity and extent of muscle involvement. This will also give an idea of the response to treatment. This test uses a magnetic field and radio waves to produce images of body tissues. During the procedure the patient lies on a bed surrounded by a metal cylinder (the scanner).

* Muscle biopsy at the beginning of the study to diagnose muscle inflammation and again at week 16 to evaluate the response to treatment.

* Electromyography if the patient has not had an EMG previously. For this test, small needles are inserted into the muscle to assess the electrical activity of the muscle

* HIV test.

Patients whose disease worsens with treatment or who develop serious drug-related side effects will be taken off the study and referred back to their primary care physician for further therapy. Patients who improve will be referred back to their primary physician at the end of the study for possible continued treatment. Participants will be asked to return for follow-up visits every 6 weeks for a total of 30 weeks to monitor long-term effects of the drug

Study Type: Interventional

Study Design: Treatment, Safety/Efficacy

Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial of Infliximab in Patients with Dermatomyositis and Polymyositis

Further Study Details: Tumor necrosis factor (TNF), a cytokine that has been implicated in the pathogenesis of many diseases including inflammatory disorders, has been found to be elevated in the muscles of patients with dermatomyositis (DM) and polymyositis (PM). A subset of patients with DM and PM do not respond readily to conventional therapy. Therefore, a controlled trial using infliximab, a chimeric IgG(1) kappa monoclonal antibody against TNF, may provide a therapeutic option and advance understanding in the pathogenesis of these diseases. This study is designed to determine the safety and efficacy of infliximab in patients with DM and PM. We plan to enroll a maximum of 28 patients randomized at 1:1 ratio into 2 groups, placebo vs. infliximab at 5 mg/kg body weight. In the first phase of the study the placebo and infliximab infusions will be given at week 0, 2, 6, and 14. Primary outcome assessment will be done at week 16. Those who respond according to the criteria set for improvement in MMT will be given the option to remain on the same infusion (i.e. placebo or infliximab at 5 mg/kg body weight) at week 22, 30, and 38. Placebo non-responders will be given infliximab at 5 mg/kg body weight in an open label fashion at weeks 16, 18, 22, 30, and 38. Patients who are initially on 5 mg/kg body weight of infliximab who failed to respond based on the criteria set will be placed on infliximab at 7.5 mg/kg body weight in an open label fashion on weeks 22, 30, and 38. Pharmacokinetic modeling will be done in both phases of the study. A muscle biopsy will be done before treatment and again at 16 weeks of treatment. Microarray gene expression profiling of the muscle biopsy specimens will be done before treatment and again at 16 weeks. Clinical, functional, and serological evaluations will be performed in every visit to assess other responses to treatment. Patients will be followed for 30 weeks after study termination to evaluate the long-term effects of the drug.

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