5 Clinical Trials for Various Conditions
Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome defined by consistently low CD4 T cell counts (\<300/mm3) without evidence of HIV infection or other known immunodeficiency. Patients with ICL are at risk for opportunistic infections typically associated with HIV/AIDS such as disseminated cryptococcal infection and severe human papillomavirus-related dysplasia. More than 20 years since the description of ICL, its etiology, pathogenesis, and management remain unclear. In this study we propose to administer the combination of granulocyte colony stimulating factor (G-CSF) and plerixafor to ICL patients and healthy volunteers with the objective of harvesting mobilized CD34+ hematopoietic progenitor cells (HPCs) by apheresis for transfer into immunocompromised mice and for study with in vitro assays. The mice studies would serve to investigate thymic development, survival, and trafficking of the mobilized human cells within murine lymphoid and non-lymphoid organs. HPCs are used for various therapies and there is an increasing use of agents that stimulate the bone marrow to produce progenitor cells and move them into the bloodstream where they may be harvested by apheresis. Not all patients respond to GCSF with vigorous HPC mobilization. The binding of chemokine receptor CXCR4 to stromal cell derived factor (SDF-1 or CXCL12) is an important interaction between a hematopoietic progenitor cell and its marrow environment. Plerixafor is a CXCR4 inhibitor which blocks binding to SDF-1 resulting in the release of hematopoietic progenitor cells (CD34+) into peripheral circulation. In pharmacodynamic studies of plerixafor in conjunction with G-CSF compared to G-CSF and placebo, a two-fold increase in CD34+ cell count was observed. Due to the important role CXCR4 plays in immune cell trafficking and its potential role in the pathogenesis of ICL, we propose as a secondary objective to assess peripheral CD4 T cell and CD34+ hematopoietic progenitor cell numbers and functions in ICL patients compared to controls following G-CSF and plerixafor administration. Study participants will be screened within 12 weeks prior to the study period. Eligible participants will receive G-CSF for 5 days with hospitalization on Day 4 for plerixafor injection followed by apheresis on Day 5. Participants will return for examinations and blood draws on Days 8 and 12.
Background: * Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic infections or autoimmune disorders and diseases. Objectives: * To characterize the natural history with regard to CD4+ T cell count and onset of infection, malignancy, and autoimmunity. * To describe the immunological status of patients affected by ICL while providing the best possible standard therapy to eradicate opportunistic infections. * To establish the timeline of CD4 lymphocytopenia, with particular focus on defining subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell counts over time. * To characterize the opportunistic infections that occur in ICL patients at microbiologic and molecular levels. * To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL. * To determine whether measurable immunologic parameters correlate with the development of opportunistic infections or other comorbidities such as lymphoma in patients with ICL. * To determine whether there is any association between ICL and autoimmunity. * To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness in ICL patients. Eligibility: * Patients 2 years of age and older with an absolute CD4 count less than 300 in children 6 years or older and adults or less than 20% of T cells in children younger than 6 on two occasions at least 6 weeks apart. * Patients with negative results of HIV testing by ELISA, Western Blot, and viral load. * Patients must not have underlying immunodeficiency conditions, be receiving cytotoxic chemotherapy (anti-cancer drugs that kill cells), or have cancer. Design: * At the initial visit to the National Institutes of Health, the following evaluations will be conducted: * Personal and family medical histories. * Physical examination, including rheumatology evaluation and other consultations as medically indicated (e.g., dermatology, pulmonology, ophthalmology, imaging studies). * Blood samples for analysis of red and white blood cell counts, liver function, immune hormones, and antibody and autoantibody levels, white blood cell growth and function, and DNA. * Urinalysis and urine pregnancy testing for female patients of childbearing age. * Evaluation and treatment of active infections as medically indicated, including biopsies, buccal swabs, pulmonary function tests, and imaging studies. * Follow-up visits will take place approximately every 12 months or more frequently if indicated, and will continue for a minimum of 4 years and a maximum of 10 years. * Evaluations at follow-up will include blood samples (i.e., CBC with differential, biochemical profile, HIV testing, etc.) and urinalysis and rheumatology consults.
Background: * Idiopathic CD4 lymphocytopenia (ICL) is a condition in which patients have low levels of T cells, a type of white blood cell that helps fight infection. Animal studies have shown that an experimental drug Interleukin 7 (IL-7), which is named CYT107, can increase the number and function of T cells. CYT107, however, has not been used in people with ICL. Objectives: * To determine the safety of CYT107 in people with ICL. * To determine whether CYT107 will increase the number and function of T cells in people with ICL. Eligibility: * Patients 18 years of age and older diagnosed with ICL and who are at risk of becoming sick because of this condition are eligible for this study. In addition, patients must not be pregnant, or have other illnesses that would cause low CD4 T cell counts, such as human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV) infection. Design: * The initial screening visit will include the following examinations and tests: * A complete physical exam and medical history * Blood analysis, including CD4 T cell count; complete blood count and additional blood tests to determine clotting ability and blood composition; thyroid, liver, kidney, and pancreatic function tests; HIV and HTLV tests; and tests for anti-IL-7 antibodies that block normal IL-7 activity * Routine urine test * Urine or blood pregnancy test for women * Chest X-ray * Electrocardiogram * Spleen ultrasound. * The baseline visit will include blood tests to determine levels of each of the major types of antibodies, a test of genetic background, and more detailed CD4 and protein analysis. In addition, leukapheresis (a procedure to collect large numbers of immune cells without red blood cells) will be done. Participants will also have the option of having colon and lymph node biopsies. * The schedule will be as follows: * Weeks 1, 2, and 3 (Cycle 1): Three weekly IL-7 dosing visits. * Weeks 5, 8, and 12: Follow-up visits. * Weeks 24, 25, and 26 (Cycle 2): Three more weekly IL-7 dosing visits. * Weeks 28, 31, and 35: Follow-up visits. * Week 48: End of study visit. * Tests conducted before getting IL-7 will be repeated during the IL-7 cycles and follow-up visits to compare with earlier values. Optional colon and lymph node biopsies done at baseline will be repeated 1 6 weeks prior to Cycle 2 and 1 6 weeks prior to Week 48.
Background: Diseases related to human papillomavirus (HPV) include warts, lesions, and cancers. ICL is idiopathic CD4 T cell lymphocytopenia. People with this rare disease get more HPV-related diseases than other people do. The diseases are more severe and harder to treat in people with ICL. Researchers want to see if the vaccine GARDASIL 9 can help people with ICL. Objective: To study the effects of the vaccine GARDASIL 9 in people with ICL. Eligibility: Adults ages 18-65 with ICL Healthy volunteers the same age Design: Participants will be screened with a physical exam, medical history, and blood and pregnancy tests. Participants will have a baseline visit with: * Physical exam * Medical history * Oral rinse collection. Participants will gargle a small amount of a saline solution, then spit it into a cup. * Apheresis. Blood will be removed through a needle in an arm. A machine will separate the blood and keep some parts for research. The rest will be returned to the participant through a needle in the other arm. * Examination for HPV-related disease. Female participants will have a Pap test. Researchers will collect swabs from some participants skin or genital lesions. Participants will get 3 doses of the study vaccine over 6 months as a shot in the upper arm or thigh muscle. They will repeat the screening tests each vaccine visit. Participants will record their temperature and side effects for several days after vaccinations. Participants may have visits after vaccinations. Participants will have 2 follow-up visits in the 18 months after the last vaccine. They will repeat most of the baseline tests. ...
This study will evaluate HIV-negative patients with unusually low levels of CD4+ T lymphocytes (a type of white blood cell) to learn more about the clinical symptoms, cause, immunology, and biology of this problem. CD4+ T lymphocytes play an important role in immune function, and low counts may leave people susceptible to unusual infections. CD4+ T cell deficiencies are most often associated with HIV infection. Patients 8 years of age and older with CD4+ T cell counts below 300 cells/mm3 who test negative for HIV infection by standard blood tests may be eligible for this study. Patients' family members and partners may also be enrolled to investigate the possible role of a genetic factor or exposure to some agent in this problem. Patients will be evaluated at the NIH Clinical Center at least once, and generally two or more times. The evaluations, which may be done on an inpatient or outpatient basis, will include some or all of the following tests and procedures: * Complete physical examination. * Medical history, including questions about sexual contacts, intravenous drug use, travel, blood transfusions, previous illnesses, including sexually transmitted diseases, and health of family members. * Urine test. * Blood tests for routine and research purposes, including tests for HIV, hepatitis, syphilis and other infections, evaluation of immune function, and culture for viruses in the HIV family. No more than 1 pint of blood will be drawn every 6 weeks. * Pregnancy test for women of childbearing potential. * Skin tests for tuberculosis and immune function. These tests involve injecting a small amount of the substance to be tested just under the skin and looking for a raised area 1 to 2 days later. * Apheresis. Whole blood is collected through an arm vein (similar to donating blood), and circulated through a cell separator machine, where it is spun to separate the components. The red cells are then returned to the patient either through the same needle or through a needle in the other arm, and the plasma and white cells are extracted for study. The procedure, which takes 1 to 2 hours, may be repeated up to 3 times. Family members will have 60 cc (4 tablespoons) of blood drawn to determine CD4+ T cell counts.