Infections

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Immune System Diseases

Blood and Lymph Conditions

Diseases and Abnormalities at or Before Birth

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Syndrome

Communicable Diseases

Herpes Simplex

Immunologic Deficiency Syndromes

Neutropenia

Primary Immunodeficiency Diseases

Warts

Agammaglobulinemia

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Granulocytopenia

WHIM Syndrome

No intervention

Sudha Parasuraman, MD

This natural history study is a prospective and retrospective, observational study of WHIM patients. WHIM syndrome is a rare, genetic, primary immunodeficiency disorder (a disorder in which the body's immune system does not function properly). WHIM is an acronym for some of the symptoms of the disorder - Warts, Hypogammaglobulinemia (low levels of certain antibodies), Infections and Myelokathexis (too many white blood cells in the bone marrow).This study includes 10-year retrospective (Retrospective Phase) and up to 5-year prospective (Prospective Phase) components.

Given the rarity of patients with WHIM syndrome, this study is being conducted to better understand the clinical course of untreated patients with WHIM syndrome.

The goals of this Natural History Study are to define both the frequency and diversity of WHIM syndrome by specific genetic mutation, as well as to understand the clinical course and phenotype of untreated WHIM patients.

Blood or buccal swab for the purposes of identifying a CXCR4 mutation.

A Retrospective and Prospective Natural History Study of Patients With WHIM Syndrome

Infections assessed by hospitalizations (including intensive care), antibiotic use, outpatient medical appointments and missed days of school/work.

Warts assessed by number and size of lesions, need for surgical, systemic or topical treatment and complications.

Quality of life as assessed by the quality of life instrument the 36-Item Short Form Survey (SF-36)

Quality of life as assessed by the quality of life instrument the Pediatric Quality of Life Inventory (Peds-QL)

Quality of life as assessed by the quality of life instrument the Life Quality Index (LQI)

Quality of life as assessed by the quality of life instrument the HPV Impact Profile (HIP)

X4 Pharmaceuticals

Epstein-Barr Virus Infections

Lymphoproliferative Disorders

Infectious Mononucleosis

Herpesviridae Infections

Chronic Graft Versus Host Disease

Chronic Active Epstein-Barr Virus Infection

Patients with chronic active Epstein-Barr virus.

Jeffrey I Cohen, M.D.

Epstein-Barr virus (EBV) is a member of the human herpes virus family that infects more than 95 percent of the U.S. population. Most infections occur in childhood and cause no symptoms; in adolescents and adults, EBV often causes infectious mononucleosis. It has also been associated with certain forms of cancer. Chronic Epstein-Barr virus (CAEBV) is a rare disease, primarily of children and young adults, that leads to life-threatening infections.

This study seeks to identify genetic mutations responsible for CAEBV. A secondary goal is to learn more about the natural history of CAEBV.

The study will examine blood and tissue samples from up to 50 patients (age 3 and above) with CAEBV and up to 150 of their relatives (age 1 and above). Autopsy samples may be included in the study. Up to 300 anonymous blood samples from the NIH Clinical Center Blood Transfusion Medicine will also be examined for comparison.

No more than 450 milligrams (30 tablespoons) of blood per 8 weeks will be drawn from adult patients, and no more than 7 milliliters per kilogram of blood per 8 weeks will be drawn from patients under age 18. Local health care providers will refer patients to the study and will obtain the samples. Some patients may also be seen at the NIH Clinical Center. Those patients will have a full medical history and physical examination, along with chest X-ray, blood counts, blood chemistry, EBV serologies, and viral load. Other tests, such as CT scan or MRI, may be performed if medically indicated. Patients will be asked to undergo leukapheresis.

In vitro tests on the blood or tissue samples will include analysis for proteins or genes that are involved in the immune response; cloning of portions of patient DNA; transformation of B cells with EBV; measurement of the ability of patient blood cells to kill EBV-infected cells; determination of lymphocyte subsets; and determination of antibodies to EBV or other herpes viruses.

If a genetic cause for CAEBV is found, the investigators will be available to discuss the results with patients in person or by telephone. Genetic indications of risk for other diseases will also be discussed with patients.

Patients with chronic active Epstein-Barr virus (CAEBV) have (a) an illness that began as a primary infection with EBV or markedly elevated titers of antibodies to EBV, (b) histological evidence of organ disease, and (c) elevated EBV DNA levels in the blood or EBV DNA or proteins in affected tissues. This is primarily a disease of children and young adults. Many of these patients develop hypogammaglobulinemia or pancytopenia and death is frequently due to opportunistic infections or B or T cell lymphoproliferative disease. The primary goal of this study is to identify genetic mutations responsible for CAEBV. The secondary goal of this study is to learn more about the natural history of CAEBV. Blood samples or available tissues (e.g. previous biopsy or autopsy material) from patients with CAEBV and their relatives will be analyzed to identify disease genes that are mutated in this population. In addition, some of the patients will be invited to come for evaluation at the NIH Clinical Center. At that time medically indicated studies of disease progression will be performed. Serial virologic and immunologic studies will be performed. Eligible relatives of patients will be studied to compare the gene(s) associated with CAEBV in patients with the gene(s) in their relatives. Knowledge gained from this study has the potential of providing insights into the immunologic control of EBV infections. In addition, identification of the molecular mechanisms for CAEBV may provide insights leading to improved treatments for this disease.

Genetic Studies of Chronic Active Epstein-Barr Disease

Genetic Studies of Chronic Active Epstein-Barr Virus Infection

Provide insights into the immunologic control of EBV infections.

Identification of the molecular mechanisms fro CAEBV.

National Institute of Allergy and Infectious Diseases (NIAID)

Musculoskeletal Diseases

Nervous System Diseases

Fatigue

Fatigue Syndrome, Chronic

Muscular Diseases

Encephalomyelitis

Neuroinflammatory Diseases

Neuromuscular Diseases

Chronic Disease

Disease Attributes

All Drugs and Chemicals

Anti-Infective Agents

Antibodies

Immunoglobulins

Valganciclovir

Antiviral Agents

valganciclovir

Jose G Montoya, MD

The purpose of this study determine whether the drug valganciclovir has a significant and real benefit on the central core of symptoms experienced by patients who have high titers to EBV and HHV-6 and are experiencing long-standing fatigue and cognitive impairment (CFS).

In addition, to characterize a quantifiable biological marker in these patients that will facilitate the identification of those likely to respond to valganciclovir and will make it possible to assess response to treatment.

Chronic fatigue syndrome (CFS) is a clinically defined condition characterized by severe disabling fatigue and a combination of symptoms that prominently features self-reported impairment of concentration and short-term memory, sleep disturbances, and musculoskeletal pain. Prevalence of CFS in the adult population is estimated to be 0.007% to 2.8%. No pathognomonic signs or diagnostic tests for this condition have been yet validated in scientific studies; in addition, no definitive treatments are clinically available. Suggested etiologies of CFS include, but are not limited to: viral or bacterial infections, endocrine-metabolic dysfunction, immunological imbalance, neurally-mediated hypotension and depressioN. EBV and HHV-6 are among the viruses frequently thought as associated with CFS.

We recently encountered a group of patients at Stanford who were chronically infected with human herpes virus 6 (HHV-6) and Epstein-Barr virus (EBV), were suffering from debilitating fatigue for at least one year and experienced a significant improvement in their fatigue and cognitive symptoms following the administration of valganciclovir. Their antibody titers to both viruses were high (median antibody titer for EBV viral capsid antigen was 1:2560 and for HHV-6 IgG was 1:1280) despite the fact that some of them were known to have been infected with EBV and HHV-6 for several years. We suspected that their symptoms could be the result of an immune dysregulation triggered by high levels of replication of both EBV and HHV-6 (alterations in the immune system such as an aberrant cytokine profiles have been proposed as the central abnormality in patients with CFS associated with other viruses such as parvovirus B19. At the same time, we were familiar using valganciclovir in the context of several clinical settings including its known indications for reactivation of viral infections in immunocompromised patients. We were comfortable using valganciclovir (900 mg bid for three weeks followed by 900 mg qd to complete 3 to 12 months of treatment) in patients with solid and bone marrow transplants, cancer or other immunosuppressive disorders who had developed CMV, EBV, or HHV-6 disease.

We hypothesized that a long course (i.e. 6 months) of valganciclovir could effectively decrease or stop ongoing viral replication of both EBV and HHV-6 and that this virological effect could be translated in a clinical and laboratory benefit (i.e. decrease or resolution of lymphadenopathy, reversion of the CD4/CD8 ratio abnormalities). We were surprised to see that a dramatic recovery on the level of physical activity was also observed in the Stanford patients (from a median of 10% of energy level for daily activities at baseline to 90% after valganciclovir use). Of note, the drug has also been tried in patients in whom an improvement on their level of physical activity has not been observed. The total number of patients treated today is 30, 26 had "elevated titers" and 4 had "low titers". Of the 26 patients with "elevated titers", 25 have had a dramatic recovery. Of the 4 patients with "low titers", none have responded.

We believe that our successful experience with valganciclovir in a subset of patients with CFS at Stanford calls for a prospective study to exclude a placebo effect. We propose to measure viral, immunologic, and genomic endpoints to assess whether there are objective and measurable changes in these parameters and whether they correlate with clinical improvement. Clinical improvement will be assessed by objective measurements of daily physical and psychological activities. This will help to elucidate the possible role of HHV-6, EBV (or a yet to be known virus) and/or an altered immune system as triggers for the symptoms experienced by patients suffering CFS and to establish whether the drug valganciclovir does reverse these abnormalities. This study may also shed light on a biomarker or profile of biomarkers associated with (or diagnostic of) CFS.

We will be executing a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of valganciclovir in patients experiencing chronic fatigue syndrome with elevated antibody titres against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV)

Objectives

1. To determine whether the drug valganciclovir has a significant and real benefit on the central core of symptoms experienced by patients who have high titers to EBV and HHV-6 and are experiencing long-standing fatigue and cognitive impairment (CFS).
2. To characterize a quantifiable biological marker in these patients that will facilitate the identification of those likely to respond to valganciclovir and will make it possible to assess response to treatment.

Design of the study A double-blind, placebo-controlled, randomized clinical trial. All patients will be given the active drug (20 patients) or placebo (10 patients) for 6 months and followed for an additional 3 months. Patients on the placebo arm will take a valganciclovir look-alike tablet that does not contain the active drug for the initial six month period. Subsequently these patients will be offered a 6 month trial of valganciclovir if at the end of the study (when the last enrolled patient reaches 9 months from initiating therapy) it is clear that there is a benefit of valganciclovir therapy and patients have not spontaneously improved.

Kogelnik A, Rosso F, Hoegh-Petersen M and Montoya JG. Use of Valganciclovir in Patients Chronically Co-infected with Human Herpes Virus 6 (HHV-6) and Epstein-Barr Virus (EBV) who were Experiencing Long-standing Fatigue. J Clin Virol 2006 Volume 37, Supplement 1 S33-S38

Kerr JR, Cunniffe VS, Kelleher P, Bernstein RM and Bruce IN. Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome. Clin Infect Dis 2003;36:e100-6

Valganciclovir (Valcyte) for Chronic Fatigue Syndrome Patients Who Have Elevated Antibody Titers Against Human Herpes Virus 6 (HHV-6)and Epstein-Barr Virus (EBV)

A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Valganciclovir (Valcyte) in Patients Experiencing Chronic Fatigue Syndrome With Elevated Antibody Titers Against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Retrospective and Prospective Natural History Study of Patients With WHIM Syndrome	NCT03087370	WHIM Syndrome	No intervention	-	X4 Pharmaceuticals
Genetic Studies of Chronic Active Epstein-Barr Disease	NCT00032513	Chronic Active ...		1 Year - 120 Years	National Institutes of Health Clinical Center (CC)
Genetic Studies of Chronic Active Epstein-Barr Disease	NCT00032513	Chronic Active ...		1 Year - 120 Years	National Institutes of Health Clinical Center (CC)
Valganciclovir (Valcyte) for Chronic Fatigue Syndrome Patients Who Have Elevated Antibody Titers Against Human Herpes Virus 6 (HHV-6)and Epstein-Barr Virus (EBV)	NCT00478465	Chronic Fatigue...	valganciclovir	18 Years -	Stanford University

Spots Global Cancer Trial Database for herpes

Every month we try and update this database with for herpes cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for herpes

Every month we try and update this database with for herpes cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for herpes cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.