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NCT ID: NCT01369927 Completed - Immunogenicity Clinical Trials

Shigella Sonnel O-SPC/rBRU Conjugate Vaccine

Start date: May 15, 2011
Phase: Phase 1
Study type: Interventional

The active ingredient of this Shigella sonnei O-SP-core conjugate vaccine is a saccharide-protein conjugate composed of a fragment of S. sonnei LPS. The saccharide component consists of an average of 3.5 repeat units of the O-SP plus the core region of the LPS (O-SPC). The O-SPC is covalently bound to the recombinant non-toxic exoprotein B of Clostridium difficile. The objective of this phase of the study is to determine if this vaccine is safe and can induce IgG antibody type-specific immunity to shigellosis in adults. The overall objective is to determine if this vaccine can elicit higher levels of IgG antibody than the previous experimental vaccines made with the full length O-SP, shown to be >70% efficacious in greater than or equal to3 year old children, to induce type-specific immunity to shigellosis in younger children. Sixty 18-49 years-old healthy adults will be recruited in Israel. Volunteers will be vaccinated on a random basis with one i.m. injection of 10 or 25 micrograms of the investigational conjugate vaccine. Local and systemic reactions will be observed at 30 minutes, and the volunteers will be instructed to take their temperature and examine the injection site for redness and swelling and fill out a questionnaire at 6, hours and daily for 7 days after vaccination. The volunteers will visit the clinic at 24 or 48 hours following the injection and any time they request it. The study will commence with 5 volunteers injected with the 10ug dose to be followed, if no severe adverse reactions occur, by 5 volunteers injected with the 25ug dose. If a severe adverse reaction occurs on 1 of the 5 volunteers in either group, 5 more will be injected with that dose. If there are no severe adverse reactions the study will proceed. If there is one more severe reaction the study will be halted and re-evaluated by the IRB and the FDA. Vaccine-induced antibodies will be measured at 1 and 6 months after immunization, and compared to those elicited by our previous S. sonnei conjugate vaccines. There is a body of evidence that a critical level of serum IgG antibody to the O-specific polysaccharide domain of LPS confers type-specific immunity to S. sonnei as well as to other Shigella: 1. Shigellosis is rarely observed in infants up to the age of 4-6 months. The most obvious explanation for this is that maternally-derived serum IgG provides this immunity; 2. There is an age-related development of IgG anti-LPS antibodies that, in many instances, is not induced by the homologous bacteria but by non-pathogenic cross-reacting enteric bacteria; 3. The highest incidence, morbidity, and mortality occur during 6 months to 6 years of age when the maternally-derived serum anti-O-SP has waned and the naturally-derived antibodies have not yet appeared; 4. One injection of a S. sonnei-rEPA conjugate showed significant protection against shigellosis in Israeli Defense Force soldiers. Vaccinees who developed shigellosis showed significantly lower serum IgG responses to the homologous LPS than those did not.The high antibody level induced by the conjugate vaccine indicates the positive correlation between the serum IgG anti-LPS levels and immunity to S. sonnei infection; 5. Following Phase 1 and Phase 2 studies that showed safety and age-related immunogenicity, a double-blinded randomized and vaccine-controlled Phase 3 evaluation of S. sonnei and S. flexneri type 2a O-specific polysaccharide (O-SP) protein conjugates was conducted among 1-4 year-olds in Israel. For recipients of the S. sonnei conjugate 71.1% efficacy was shown among 3-4 year-old recipients, no efficacy was shown for recipients of S. flexneri 2a. There was no statistically significant efficacy for either vaccine in the 1-3 year-olds. Levels of serum IgG anti-O-SP were elevated according to the vaccine the children received but G.M. levels declined rapidly several months after the last injection. Our interpretation is that the age-related efficacy of the Shigella conjugates was due to the conjugate-induced O-SP antibody levels. Accordingly, we have developed a method to increase the immunogenicity of the conjugates to approach the antibody levels of Israeli soldiers shown to be protected by our S. sonnei O-SP. Low-molecular-mass O-SP-core (O-SPC) fragments were isolated from S. sonnei LPS, and bound by their reducing ends to the carrier protein. The O-SPC conjugates used oxime linkages between the terminal Kdo residues at the reducing ends of the S. sonnei saccharides and aminooxy linkers bound to the carrier. The coupling reaction was carried out at a neutral pH and room temperature. The carrier protein was a mutant non-toxic Clostridium difficile exotoxin B. IgG antibody levels induced in young outbred mice by this new S. sonnei O-SPC conjugate were significantly higher than those elicited by the O-SP conjugates.

NCT ID: NCT01369615 Completed - Pain Clinical Trials

Long-Term Safety of Twice Daily Oxycodone Hydrochloride Controlled-release Tablets in Children Who Completed OTR3001

Start date: October 2011
Phase: Phase 3
Study type: Interventional

The purpose of this study is to characterize the long-term safety of oxycodone hydrochloride (HCl) controlled-release (CR) tablets in opioid experienced pediatric patients aged 6 to 17 years, inclusive, with moderate to severe malignant and/or nonmalignant pain requiring opioid therapy who completed the 4 -week treatment period in OTR3001.

NCT ID: NCT01369355 Completed - Crohn's Disease Clinical Trials

A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients With Moderately to Severely Active Crohn's Disease (IM-UNITI)

Start date: September 13, 2011
Phase: Phase 3
Study type: Interventional

The primary purpose of this study is to evaluate the efficacy and safety of 2 maintenance regimens of ustekinumab administered subcutaneously to patients with moderately to severely active Crohn's disease who responded to treatment with intravenous ustekinumab in studies CNTO1275CRD3001 and CNTO1275CRD3002, compared to subcutaneously administered placebo.

NCT ID: NCT01369342 Completed - Crohn's Disease Clinical Trials

A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Patients With Moderately to Severely Active Crohn's Disease (UNITI-2)

Start date: July 2011
Phase: Phase 3
Study type: Interventional

This study (UNITI-2) will compare the effects (both positive and negative) of an initial treatment with ustekinumab to a placebo over 8 weeks in patients with moderately to severely active Crohn's disease.

NCT ID: NCT01369329 Completed - Crohn's Disease Clinical Trials

A Study to Evaluate the Safety and Efficacy of Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease Who Have Failed or Are Intolerant to Tumor Necrosis Factor (TNF) Antagonist Therapy (UNITI-1)

Start date: July 2011
Phase: Phase 3
Study type: Interventional

This study (UNITI-1) will compare the effects (both positive and negative) of an initial treatment with ustekinumab to placebo over 8 weeks, in patients with moderately to severely active Crohn's disease who have either failed or could not tolerate at least one TNF-antagonist medications in the past (specifically, infliximab, adalimumab, or certolizumab pegol).

NCT ID: NCT01368588 Active, not recruiting - Prostate Cancer Clinical Trials

Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients With Prostate Cancer

Start date: July 2011
Phase: Phase 3
Study type: Interventional

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens. Radiation therapy uses high-energy x-rays to kill tumor cells. PURPOSE: This randomized phase III trial studies androgen-deprivation therapy and radiation therapy in treating patients with prostate cancer.

NCT ID: NCT01368302 Completed - Clinical trials for Attention Bias Modification Treatment (ABMT)

Attention Bias Modification Treatment (ABMT) for Patients With Post Traumatic Stress Disorder (PTSD)

Start date: July 2011
Phase: Phase 2
Study type: Interventional

Patients with Post Traumatic Stress Disorder (PTSD) will be randomly assigned to either Attention Bias Modification Treatment (ABMT) designed to normalize threat-related attention biases or a placebo control condition not designed to change attention patterns. Outcome measures will be Post Traumatic Stress Disorder (PTSD), depression, and anxiety symptoms as measured by gold standard questionnaires and symptom counts derived from structured clinical interviews. We expect to see significant Post Traumatic Stress Disorder symptom reduction in the Attention Bias Modification Treatment (ABMT) group relative to the placebo control group in which no symptomatic relief is expected.

NCT ID: NCT01367782 Recruiting - Clinical trials for Asymmetric Parkinson's Disease

A Double Blind Sham-controled Study to Evaluate the Influence of Low Frequency Repetitive Transcranial Stimulation (r-TMS) on Motor and Cognitive Measurements in Patients With Asymmetric Parkinson's Disease

Start date: May 2011
Phase: N/A
Study type: Interventional

The purpose of this study is to test the effects of low frequency deep rTMS using the novel H-coil on the motor, affective and cognitive deficits in patients with asymmetric Parkinson's disease (PD), to establish its safety in this population and to test effects of maintenance treatments.

NCT ID: NCT01367665 Completed - Clinical trials for Basal Cell Carcinoma

STEVIE: A Study of Vismodegib in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma

Start date: July 1, 2011
Phase: Phase 2
Study type: Interventional

This single-arm, open-label, multi-center study will evaluate the safety and efficacy of vismodegib (GDC-0449) in patients with locally advanced or metastatic basal cell carcinoma. Patients will receive oral doses of vismodegib 150 mg once daily until disease progression or unacceptable toxicity.

NCT ID: NCT01367639 Completed - Clinical trials for Hereditary Breast and Ovarian Cancer Syndrome

Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers

Start date: March 2011
Phase: Phase 2
Study type: Interventional

Breast cancer (BC) is a major health problem and the most prevalent cancer among women.In a substantial proportion of familial cases, germ-line mutations in either BRCA1/2 can be detected. The only proven modality for active risk reduction (rather than passive early detection), is prophylactic surgery - prophylactic mastectomy and oophorectomy. While the majority of Jewish mutation carriers elect to undergo prophylactic oophorectomy at about age 40 years, in Israel only a minority perform prophylactic mastectomy. Another ramification of being a mutation carrier is the emotional stress associated with that discovery.Genetic information has profound implications for mutation carriers. The IBSR (Inquiry-based stress reduction) intervention, developed by Byron Katie, trains participants to reduce their perceived level of stress by self-inquiry of their thoughts and beliefs connected to stressful circumstances or symptoms. This meditative process, named "The Work", enables the participants to identify and question the stressful thoughts that cause their suffering. The core of IBSR is simply four questions and a turnaround, which is a way of experiencing the opposite of what the participant believes. This process is simple, powerful and provides skills for self-inquiry and management of stressful thoughts that can be easily implemented in daily life [ ]. Therefore, on the basis of previous data and beneficial observations we postulate that the clinical utility of IBSR mediation program may improve psychological and physical symptoms and quality of life among asymptomatic (oncologically healthy) BRCA1/ BRCA2 mutation carriers. Thus, we will conduct a pilot randomized controlled trial to scientifically investigate the effect of this intervention effects on BRCA1/2 mutation carriers.