Infections

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Blood and Lymph Conditions

Diseases and Abnormalities at or Before Birth

Immune System Diseases

Rare Diseases

Communicable Diseases

Crohn Disease

Intestinal Diseases

Inflammatory Bowel Diseases

Necrosis

Granulomatous Disease, Chronic

Granuloma

Gastrointestinal Diseases

Gastroenteritis

Lymphoproliferative Disorders

Lymphatic Diseases

Phagocyte Bactericidal Dysfunction

Leukocyte Disorders

Hematologic Diseases

Genetic Diseases, X-Linked

Genetic Diseases, Inborn

Syndrome

Immunologic Deficiency Syndromes

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Granulomatous Disease

Anti-Inflammatory Agents

Antirheumatic Agents

All Drugs and Chemicals

Dermatologic Agents

Gastrointestinal Agents

Adalimumab

Infliximab

Tumor Necrosis Factor Inhibitors

Study drug (TNFa inhibitor-infliximab or adalimumab) treated group.

Subjects with IBD without TNFa inhibitor treatment

Suk S De Ravin, M.D.

This study will determine if the drug infliximab is safe for treating inflammatory bowel disease (IBD) in patients with chronic granulomatous disease (CGD). IBD is an inflammation or irritation of the gut that leads to symptoms such as diarrhea, bloating and stomach cramps. CGD is an inherited disease affecting white blood cells called neutrophils in which patients are susceptible to repeated bacterial and fungal infections. They also have a higher incidence of some autoimmune diseases, such as IBD. Infliximab is approved to treat Crohn's disease, an IBD similar to that seen in patients with CGD.

Patients 10 years of age and older with CGD and IBD may be eligible for this study. Candidates are screened with a medical history, physical examination, blood and urine tests, electrocardiogram (EKG), tuberculosis skin test (PPD skin testing), and stool test for the presence of infections. Additional tests may be done, including colonoscopy (procedure using a flexible tube through the rectum to examine the lining of the gut) and imaging studies such as an x-ray, chest CT scan (test using a special x-ray machine), MRI (test using a magnetic field and radio waves), and barium studies (study using a drinkable solution of barium to help enhance the x-ray pictures of the gut).

Participants are divided into patients with IBD symptoms (Group 1) and patients without IBD symptoms (Group 2) for the following procedures:

Group 1

Patients are evaluated every 6 months with a medical history and physical examination for signs and symptoms of IBD. Patients who are taking moderate to high doses of steroid medications have their medication slowly lowered (tapered) and are evaluated every 3 months for a total of 2 years. Patients in this group who start to develop IBD symptoms are moved to Group 2 for treatment with infliximab (see below).

Group 2

Patients in Group 2 receive infliximab infusions at 2-week intervals for three doses. The drug is given over a 2-hour period through a catheter placed in a vein. Patients are evaluated with a medical history, physical exam, and blood tests the day of each dose. One week after the last dose, they have another evaluation, including a colonoscopy. Patients who respond well to infliximab may continue to receive the drug every 2 months for a total of 1 year, with evaluations at every dosing visit. At the end of the first year of receiving infliximab, all patients have follow-up evaluations every 6 months for a total of 2 years.

Group 3

Subjects who volunteer to undergo colonoscopy and research biopsies that serve as controls for evaluation of the patient gut samples.

Chronic Granulomatous Disease (CGD) is an inherited immune disorder involving decreased phagocytic superoxide oxygen radical production, resulting in increased susceptibility to infections. Furthermore, there is a predominance of immune-related inflammatory problems in a subset of CGD patients, such as the inflammatory bowel disease (CGD-IBD). CGD-IBD is often complicated by obstruction, strictures, fissures, fistulae, and extra-intestinal problems. In fact, it is clinically and histologically indistinguishable from Crohn's Disease (CD), another inflammatory bowel disease that affects the general population. Crohn's disease (CD) is a prototypic T helper cell type 1 (Th1) immune disease. Since CGD-IBD bears such close resemblance to CD, it is possible that CGD-IBD is also immune-based. Furthermore, mice studies also support a primarily immune basis for CGD-IBD. However, currently there is little data on this Crohn's-like CGD-IBD in human patients. Treatment for the Crohn's-like CGD-IBD has been primarily oral or topical corticosteroids. Antibiotics have been ineffective and stool cultures typically do not identify clear pathogens. Many patients with the Crohn's-like CGD-IBD disease remain steroid-dependent, thus new therapeutic regimens are needed.

This is a Phase I/II study that will evaluate the safety and efficacy of Tumor Necrosis Factor Alpha Inhibitor (Infliximab or Adalimumab) in CGD patients with symptomatic Crohn's-like IBD. Infliximab and Adalimumab are standard-of-care treatments for moderate to severe CD, with extensive experience using these agents being well documented in terms of safety and efficacy. Preliminary reports from ongoing studies of CD at NIH are encouraging in inducing remission. We will also evaluate changes in immunophenotype and cytokine profiles of peripheral blood and colonic lamina propria lymphocytes following treatment. In addition, we will evaluate the immunophenotype and cytokine profile of blood and mucosal cells in CGD patients, with or without IBD, to determine the CGD-specific cytokine profile. Specific cytokine profiles have been observed in different genetic immunodeficiencies, despite similar IBD clinical manifestation.

Documentation of clinical status will be performed using the Crohn's Disease Activity Index (CDAI). Potential effects of genetic variation (including CGD mutation type) on the expression of IBD in patients with CGD, and their responses to treatment will also be assessed. The long-term goal of this study is to establish better or alternative treatment modalities with low risk profiles for CGD patients with Crohn's-like IBD.

Infliximab to Treat Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease

Tumor Necrosis Factor Alpha Inhibitor (Lnfliximab, Adalimumab) Treatment for Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease: A Phase I/II Study Assessing Clinical and Immune Responses to Treatment and Genetic Influences

Gut Immune cell types and their cytokine profile

Number of Infections from Baseline to 1 year

Measured participant Crohn's disease Activity Index (CDAI) values. The CDAI is a tool comprised of clinical and laboratory factors such as stool frequency, consistency, abdominal pain, general well being, weight and blood profile as an objective measure of disease activity. A higher score corresponds to greater severity of inflammatory bowel disease; severe disease conventionally defined as \>450, a remission as \<150, and a response to treatment as a fall of CDAI of \>70 points. Infections and IBD are not expected in healthy control subjects. The greater the score, the more severe the disease, and a score of less than 5 represents clinical remission.

National Institute of Allergy and Infectious Diseases (NIAID)

The adverse events reported only relate to events occurring following study drug (TNFa inhibitors) treatment. Group 3 subjects who volunteered for endoscopy/gut biopsies are terminated at completion of the procedure. Baseline infections in endoscopy volunteers are not reported as adverse events.

This group comprises patients with Chronic granulomatous disease (CGD) complicated by significant inflammatory bowel disease (IBD). The subjects are treated with a TNFa inhibitor at standard recommended doses for treatment of Crohn's disease. Infliximab is administered as intravenous infusions at 5mg/kg on weeks 0, 2 and 6 for induction and every 6-8 weeks at 5-10mg/kg for maintenance. Adalimumab is administered at 160mg, 60mg, 40mg, 40mg on weeks 0, 2, 4 and 6 via subcutaneous injection.

Endoscopies and gastrointestinal mucosal biopsies are obtained before treatment, following induction, and again at completion of treatment.

Treatment Group

CGD patients with IBD who are not treated with any study medication and are monitored for rate of infections.

Observation Group

Subjects who volunteer to participate in endoscopy and GI mucosal biopsies to provide controls for the study. The subjects in this arm may be healthy subjects, CGD subjects without GI symptoms, or subjects with Crohn's disease (CD). The rate of infections in the CGD patients without IBD are monitored.

Control Volunteer

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Due to limited subject participation and lack of sustained clinical benefits (1 year), there is insufficient complete data to generate meaningful statistics for the outcome measures. Instead, this data are reported as a case series.

De Ravin, SukSee

Treatment

Observation

Control Volunteers

The volunteer group includes patients with chronic granulomatous disease as well as healthy normal volunteers as controls. Infection rates only pertain to and are counted in subjects with underlying immunodeficiency (chronic granulomatous disease).

Safety of Study Drug

CDAI Value #1 at Baseline

CDAI Value #2 at Baseline

CDAI Value #3 at Baseline

CDAI Value #4 at Baseline

CDAI Value #5 at Baseline

CDAI Value #1 at 1 year

CDAI Value #2 at 1 year

CDAI Value #3 at 1 year

CDAI Value #4 at 1 year

CDAI Value #5 at 1 year

All participants in the Treatment and Observation Arms with collected CDAI data. The CDAI, a tool validated for Crohn's disease is not applicable to healthy donors or CGD patients without IBD, and therefore not measured in the Control participants.

Efficacy of Treatment With Study Drug

Gut Immune Cell Types and Their Cytokine Profile

Overall Study

Neoplasms

Nutritional and Metabolic Diseases

Nervous System Diseases

Gland and Hormone Related Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Anemia, Sickle Cell

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Anemia

Lymphoma

Metabolic Diseases

Thalassemia

Hematologic Neoplasms

Anemia, Aplastic

Metabolism, Inborn Errors

Adrenoleukodystrophy

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Sickle Cell Anemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Aplastic Anemia

Acute Graft Versus Host Disease

X-linked Adrenoleukodystrophy

Adrenomyeloneuropathy

The CliniMACS CD34 Reagent System is a medical device that is used in vitro to select and enrich CD34+ cells from heterogeneous hematologic cell populations for transplantation in cases where this is clinically indicated.

CliniMACS CD34 Reagent System

Erin Arbuckle

Joanne Kurtzberg, MD

The objective of this study is to make T-cell depleted stem cells from a family member who is a half match (haplo-identical) available on an expanded access basis to patients receiving one or two unrelated cord blood transplants who are at a higher risk of not engrafting in a safe amount of time. The purpose of the related stem cells is the give the bone marrow a "jump start" towards recovery. Ultimately, the cord blood cells will grow and permanently rescue the bone marrow.

The primary purpose of the study is to provide expanded access of T-cell depleted haplo-identical stem cells for patients receiving allogeneic transplantation from a related haplo-identical donor and an unrelated, umbilical cord blood (UUCB) unit(s) for the treatment of high risk malignancies and non-malignant disorders. The T-cell depleted haplo-identical stems cells are intended to facilitate early, short-term myeloid engraftment with the primary goal of minimizing early infections and other non-relapse mortality while the UUCB cells engraft as the durable and permanent graft. Patients with high risk or refractory malignancies, or non-malignant disorders amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors will be eligible for this protocol.

Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Haplo-Identical and Unrelated Cord Blood Transplants

A Compassionate Release Protocol: Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Allogeneic Transplantation Using a Related Haplo-Identical Donor and Unrelated, Umbilical Cord Blood Donor(s) for the Treatment of High Risk Malignancies or Non-Malignant Disorders Requiring Allogeneic Transplantation

Duke University

Miltenyi Biotec, Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Infliximab to Treat Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease	NCT00325078	Chronic Granulo... Crohn'S-like IB... Inflammatory Bo...	Infliximab	10 Years -	National Institutes of Health Clinical Center (CC)
Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Haplo-Identical and Unrelated Cord Blood Transplants	NCT01881334	Hematologic Mal... Inborn Errors o... Immune Deficien...	CliniMACS CD34 ...	- 65 Years	Duke University

Spots Global Cancer Trial Database for cgd

Every month we try and update this database with for cgd cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for cgd

Every month we try and update this database with for cgd 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 cgd 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.