Clinical Trials News

Nicotine And Dementia

2008-07-14T16:31:00.000-07:00

Alzheimer's Society comment on a review of research studies investigating nicotine and dementia, which have been conducted over the last 5 years

'Nicotine has previously been shown to help treat Alzheimer's disease in animal studies. This new review brings together evidence to explain the processes behind this and which types of nerve cells nicotine effects in the brain.

Although nicotine has therapeutic qualities, when it is absorbed through smoking the health risks outweigh the benefits. Smoking increases risk of vascular dementia, the second most common form of dementia and is associated with a number of other health risks.

More research is now needed to find a safe and effective treatment for dementia, with the potential benefits of nicotine, but without the health risks.'

INTUNIV Showed Significant Efficacy In Reducing ADHD Symptoms

2008-05-08T14:28:00.000-07:00

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Shire plc(LSE: SHP, Nasdaq: SHPGY), the global specialty biopharmaceutical company, has presented at a major scientific meeting findings from analyses of pivotal trial results of INTUNIV, a selective alpha-2A-agonist. This compound is an investigational once-daily medication, which is being evaluated for the treatment of the symptoms of Attention Deficit Hyperactivity Disorder (ADHD). The data demonstrated that INTUNIV showed significant efficacy in reducing ADHD symptoms for patients taking the medication when compared to patients taking placebo at all measured time points up to 24 hours postdose.

The U.S. Food and Drug Administration (FDA) issued an approvable letter on June 20, 2007, regarding INTUNIV. Shire is conducting additional clinical work which is designed to enhance the label. Upon approval, INTUNIV will be the first selective alpha-2A receptor agonist indicated for the treatment of ADHD that may provide an important treatment option for patients and physicians.

Summary of Analyses

The pooled analysis evaluated results from these patients on a weight adjusted mg/kg basis from two similarly designed, randomized, double-blind, forced-dose titration, multicenter phase III trials. The primary efficacy measure for both studies was change in the ADHD Rating Scale (ADHD-RS-IV) total score from baseline to endpoint. All patient groups treated with INTUNIV showed significantly greater improvement in ADHD-RS-IV total score from baseline to endpoint than the placebo group (P < .001). The ADHD-RS-IV is a standardized, validated test for assessing symptoms of ADHD and for assessing their response to treatment.

The analysis also studied duration of effect using the Conners' Parent Rating Scale-Revised Short Form (CPRS-R), which is a comprehensive scale that used observer and self-report ratings to help assess ADHD and evaluate behavioral issues in children and adolescents. The CPRS-R assessments were completed on specified days at approximately 6 PM (after school and before dinner), 8 PM (dinner through bedtime) and 6 AM (waking time/new dose administration time), which represented 12, 14 and 24 hours after the administration of the dose of INTUNIV, respectively. The data demonstrated significant improvement of ADHD symptoms based on total endpoint CPRS-R scores for all weight adjusted dose groups treated with INTUNIV when compared to placebo for all time periods (at 12 hours, P < = .001; at 14 hours, P < .001; and at 24 hours, P=.003).

A separate analysis of the same phase III studies evaluated the percentage of ADHD patients who responded to weight-adjusted treatment with INTUNIV versus those participants receiving placebo. Using the change in the ADHD-RS-IV total score from baseline to endpoint as the primary efficacy measure, responders were defined as those with a 25 percent reduction in score from baseline to endpoint. Findings from the analysis showed that all groups treated with INTUNIV responded to the medication in a shorter time period than the placebo group (14 days versus 20 days, respectively, P = .001).

In the phase III studies, adverse events (AEs) were reported in 80.7 percent of patients treated with INTUNIV and 71.8 percent of patients treated with placebo. Overall, the AEs were mostly mild to moderate in severity. Adverse reactions that appeared to be dose-related in patients given INTUNIV included upper abdominal pain, constipation, dizziness, dry mouth, hypotension, sedation, and somnolence. Serious AEs reported in these analyses were uncommon and rates were similar between patients treated with INTUNIV and patients treated with placebo (0.6% of the INTUNIV group and 0.7% of placebo group, respectively).

Decompression Surgery In Patients With Cervical Spinal Cord Injuries

2008-05-03T08:58:00.000-07:00

Every year, nearly 12,000 individuals in the United States and Canada, mostly young adults, sustain a spinal cord injury (SCI). According to the Centers for Diseases Control and Prevention (CDC), SCI costs an estimated $9.7 billion each year in the United States alone. Although there are some surgical interventions, such as decompression, which neurosurgeons administer to SCI patients after injury, these procedures have not dramatically improved overall recovery and outcome

"This is an area of medicine that has not seen tremendous scientific advances, so there remains an urgent need to improve upon current interventions to help restore neurological function in patients with acute SCI," said Michael Fehlings, MD, PhD, FRCSC, FACS, head of the Krembil Neuroscience Center at the University Health Network in Toronto and professor of Neurosurgery at the University of Toronto.

Surgical decompression of the spinal cord is often done after an injury occurs, although the timing of this intervention varies widely. Surgery involves the removal of various tissue or bone fragments that are compressing and comprising the spinal cord. Depending on the unique circumstances of the injury, decompression is accomplished through a variety of surgical approaches, including, for example, approaching the compressed cord from either the front (anterior) or back (posterior).

The role and timing of decompression in patients with SCI is controversial. Despite a strong biological rationale, the clinical data to support early decompression are unconvincing. Accordingly, researchers conducted a prospective multicenter study to evaluate the role and timing of decompressive surgery in a consecutive series of patients with cervical SCI. The Surgical Treatment of Acute Spinal Cord Injury Study (STASCIS) has enrolled 170 patients to date.

The findings of this study, A Prospective Multicenter Trial to Evaluate the Role and Timing of Decompression in Patients with Cervical Spinal Cord Injury: Initial One-Year Results of the STASCIS Study, will be presented by Dr. Fehlings, 10:25 to 10:39 a.m. on Monday, April 28, 2008, during the 76th Annual Meeting of the American Association of Neurological Surgeons in Chicago. Co-authors are Bizhan Aarabi, MD, Marcel Dvorak, MD, FRCSC, Charles G. Fisher, MD, FRCSC, James Harrop, MD, Stephen Lewis, MD, Eric M. Massicotte, MD, FRCSC, Y. Raja Rampersaud, MD, Christopher Shaffrey, MD, and Alexander Vaccaro, MD; FRCSC.

Patients with cervical SCI (American Spinal Injury Association (ASIA) grades A-D) and evidence on computed tomography (CT)/magnetic resonance imaging (MRI) of canal/cord compression were entered into the prospective multicenter nonrandomized case-control study. ASIA grade 'A' designates complete SCI, and Grades 'B' through 'D' designate decreasing levels of neurological involvement. Decompression was achieved by traction and/or surgery. Additional patient demographics were as follows:

-- Males: 78.1 percent, Females: 21.9 percent

-- Mean age 42.2 (±17.3)

-- SCI severity: ASIA A (43.6 percent), B (22.3 percent), C (16.0 percent), D (18.1 percent)

Patients were stratified into "early" (less than 24 hours) or "delayed" (greater than 24 hours) groups based on time to decompression. There were no significant differences in age, gender, or ASIA level or medical comorbidities between the early and delayed groups Outcomes were assessed using the ASIA system. Traction was used in 28.6 percent of patients in the early group and 21.1 percent of patients in the delayed group. To date, six-month and one-year follow-up has been obtained in 108 and 64 cases, respectively.

At six-month follow-up, 24 percent of the patients in the early decompression group had a two-grade or greater improvement in ASIA score compared to 4 percent in the delayed group (p=0.014). "The initial results from our STASCIS research suggest that decompression within 24 hours of injury may be associated with improved neurological recovery at one-year follow-up. However, further recruitment of patients with long-term follow-up is necessary to validate these promising results," stated Dr. Fehlings.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 7,200 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.

American Association of Neurological Surgeons (AANS)
5550 Meadowbrook Dr.
Rolling Meadows, IL 60008
United States
http://www.neurosurgerytoday.org

Progesterone Could Prevent Brain Damage After Head Injury

2008-05-01T16:42:00.000-07:00

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A common component of the contraceptive pill (progesterone) could improve the neurologic outcome for patients with severe head injuries, according to a study published in BioMed Central's open access journal Critical Care.

Traumatic brain injury (TBI), such as that caused by traffic accidents, falls and sporting injuries, is a major cause of death and disability. A number of 'neuroprotective' drugs have been shown to prevent nerve-cell death in animal models of traumatic brain injury, but these findings have not been translated into trials involving people with head injuries.

Progesterone is a female hormone used in the oral contraceptive pill. Preliminary animal and human studies suggest that progesterone could be a useful and safe way to treat acute severe traumatic brain injury, but its neuroprotective effects are unclear. Now, Chinese researchers have shown that progesterone can improve the neurologic outcome of patients with this kind of brain injury for up to six months.

A research team from Hangzhou Normal University and Zhejiang University in Hangzhou, supervised by Professor Weiqi Yan, studied 159 patients with acute traumatic brain injury admitted to a single hospital. In this randomized, double-blinded trial approximately half the patients received progesterone and the other half placebo for five days after brain injury.

"Although previous studies in animal suggest that progesterone may mitigate the severity of brain damage, there is no information about therapeutic benefit of post-TBI progesterone injections in the patients with severe brain trauma" said Professor Yan. "Our work was to determine if progesterone improve chances for recovery in patients with severe injuries in a longer-term".

Patient outcomes were classified either as favourable (good recovery or moderate disability) or unfavourable (severe disability, vegetative state or death). Neurological outcomes were measured using the Glasgow Outcome Scale, a medical system for evaluating the functional outcome of patients.

At both three and six months after treatment, significantly more patients given progesterone had favourable outcomes compared to patients given placebo. Progesterone was also linked to increased survival at six months. No complications or adverse events were seen in the patients given progesterone.

"We found encouraging evidence that progesterone may significantly improve 6-month neurologic outcome of the patients who were enrolled with acute severe TBI" according to lead author, Dr Giomin Xiao. "Our results provide information important for further multicenter clinical trials on progesterone as a promising neuroprotective drug".

Cell-Based Therapy Shows Promise In Patients With Parkinson's Disease

2008-04-29T04:37:00.000-07:00

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A novel cell therapy using retinal pigment epithelial (RPE) cells attached to tiny gelatin bead microcarriers implanted in the brain can improve the symptoms of patients with moderate to advanced Parkinson's disease (PD).

Rush University Medical Center neurosurgeon Dr. Roy A. E. Bakay and colleagues from Emory University, Atlanta found the therapy Spheramine was well-tolerated and patients experienced improvement in Parkinsonian symptoms (tremor, rigidity, slowness of movements, and impaired balance and coordination.) These findings were presented at the Annual Meeting of the American Association of Neurological Surgeons in Chicago on April 28, 2008.

The pilot study was initiated at Emory University Hospital and followed six patients with moderate to advanced PD to investigate the safety, tolerability, and efficacy of the Spheramine implantation. The full patient group has been evaluated for four years, and several have been monitored for six years. Bakay and colleagues report long-term improvement or stabilization of symptoms, maintained for a minimum of two years after Spheramine implantation. They note no Spheramine-related serious adverse events were reported and that the most frequent adverse event was postsurgical headache, which spontaneously resolved within one to two weeks.

"The results of this study are very encouraging - Spheramine is well tolerated through several years of follow-up and improvement in parkinsonian symptoms is sustained," stated Bakay.

The cellular product Spheramine consists of RPE cells attached to microcarriers. RPE cells produce levodopa, the precursor of dopamine. Dopamine is a neurotransmitter produced by nerve cells in the brain that progressively declines as the disease progresses.

The RPE cells, which are normally found in the back of the eye, are cultured under standardized conditions and attached to the microscopic beads prior to implantation. The microcarriers are necessary for the cells to survive in the brain. The implanted cells serve as a new potential source of levodopa to enhance dopamine production where it is most needed.

The patients were selected based on disease stage, levodopa responsiveness, and severity of PD symptoms while off medication. An even distribution of Spheramine was surgically implanted into the more affected side of the brain, and patients left the hospital a few days later.

The primary efficacy measure in this trial is the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) when the patient has been OFF antiparkinsonian medication for at least 12 hours. The researchers report clinical improvements were noted in both UPDRS motor scores off medication (44 percent improvement from baseline at 48 months) and patient-reported quality of life scores (23 percent improvement from baseline of total PDQ-39 score at 48 months). Several of these patients have been monitored for 6 years and the trial has been extended to 10 years of follow-up."

Bakay said positive results in the pilot study prompted the initiation of a Phase IIb, multicenter, double-blind, randomized, sham surgery-controlled study (STEPS) to further evaluate the safety, tolerability and efficacy of Spheramine. Changes from the pilot study included implantation in both sides of the brain and the addition of a sham surgery group. To date, 71 patients have been randomized for either Spheramine or sham surgery and results from the will become available later this year.

Peptimmune Completes Phase I Study With A Novel Peptide Copolymer For The Treatment Of Multiple Sclerosis

2008-03-21T05:36:00.000-07:00

Peptimmune, Inc. a privately held biotechnology company, announced that it has completed its first clinical trial to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PI-2301, a novel peptide copolymer for the treatment of multiple sclerosis and other autoimmune diseases.

The Phase I single ascending dose, double blind placebo controlled randomized study involved 56 healthy volunteers who received the drug in eight escalating dose cohorts. All doses were safe and well tolerated, and there were no serious adverse events. Pharmacodynamic assays demonstrated evidence of immune exposure consistent with the pharmacologic mechanism of action for PI-2301, and dose related pharmacokinetics were observed. The Company plans to initiate its first repeat dose study in multiple sclerosis patients in Q2/2008.

"We are pleased to see that PI-2301 was well tolerated and that this trial has provided evidence of single dose priming of healthy subjects. This effect is important as repeated doses in multiple sclerosis patients should lead to therapeutic immune modulation," stated Thomas P. Mathers, President and CEO of Peptimmune. "We have designed PI-2301 to maximize the therapeutic benefit of a proven, safe compound class in multiple sclerosis as well as increasing patients' convenience."

PI-2301 is a second generation peptide copolymer from a similar compound class as Copaxone(R) (Teva Pharmaceuticals). PI-2301 works through immune modulation by enhancing the regulatory response of the immune system to control the pathogenic autoimmune response in certain diseases. PI-2301 has been optimized using Peptimmune's novel platform peptide chemistry and in pre- clinical studies, has shown to be more potent and effective than Copaxone in treating disease models for multiple sclerosis. PI-2301 has also shown efficacy in pre-clinical models of autoimmune diseases where immune modulation may be effective, such as Crohn's disease, rheumatoid arthritis and autoimmune uveitis. Peptimmune has also introduced highly reproducible manufacturing methods that allow very strict control and characterization of PI-2301 and should provide a superior level of batch to batch consistency.

Over 400,000 Americans have multiple sclerosis (MS), and worldwide MS may affect over 2.5 million individuals. MS is an autoimmune disease in which the individuals' immune system responds against multiple components of nerve- insulating myelin. The effects of these immune-mediated attacks can range from relatively benign to somewhat disabling to devastating, as communication between the brain and other parts of the body is disrupted.

Peptimmune Completes Phase I Study with a Novel Peptide Copolymer for the Treatment of Multiple Sclerosis

2008-03-18T12:44:00.000-07:00

CAMBRIDGE, Mass., March 18 /PRNewswire/ -- Peptimmune, Inc. a privately held biotechnology company, announced that it has completed its first clinical trial to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PI-2301, a novel peptide copolymer for the treatment of multiple sclerosis and other autoimmune diseases.

The Phase I single ascending dose, double blind placebo controlled randomized study involved 56 healthy volunteers who received the drug in eight escalating dose cohorts. All doses were safe and well tolerated, and there were no serious adverse events. Pharmacodynamic assays demonstrated evidence of immune exposure consistent with the pharmacologic mechanism of action for PI-2301, and dose related pharmacokinetics were observed. The Company plans to initiate its first repeat dose study in multiple sclerosis patients in Q2/2008.

"We are pleased to see that PI-2301 was well tolerated and that this trial has provided evidence of single dose priming of healthy subjects. This effect is important as repeated doses in multiple sclerosis patients should lead to therapeutic immune modulation," stated Thomas P. Mathers, President and CEO of Peptimmune. "We have designed PI-2301 to maximize the therapeutic benefit of a proven, safe compound class in multiple sclerosis as well as increasing patients' convenience."

PI-2301 is a second generation peptide copolymer from a similar compound class as Copaxone(R) (Teva Pharmaceuticals). PI-2301 works through immune modulation by enhancing the regulatory response of the immune system to control the pathogenic autoimmune response in certain diseases. PI-2301 has been optimized using Peptimmune's novel platform peptide chemistry and in pre- clinical studies, has shown to be more potent and effective than Copaxone in treating disease models for multiple sclerosis. PI-2301 has also shown efficacy in pre-clinical models of autoimmune diseases where immune modulation may be effective, such as Crohn's disease, rheumatoid arthritis and autoimmune uveitis. Peptimmune has also introduced highly reproducible manufacturing methods that allow very strict control and characterization of PI-2301 and should provide a superior level of batch to batch consistency.

Over 400,000 Americans have multiple sclerosis (MS), and worldwide MS may affect over 2.5 million individuals. MS is an autoimmune disease in which the individuals' immune system responds against multiple components of nerve- insulating myelin. The effects of these immune-mediated attacks can range from relatively benign to somewhat disabling to devastating, as communication between the brain and other parts of the body is disrupted

First Patient Implant With Artificial Cervical Disc In U.S.

2008-03-06T11:34:00.000-08:00

Spinal Kinetics, a leader and innovator in advanced generation artificial disc technology, announced that it has enrolled the first U.S. Feasibility Study patient and successfully implanted the company's M6-C artificial cervical disc. This first procedure was completed at Olympia Medical Center in Beverly Hills, California by leading spine surgeon Carl Lauryssen, M.D., from the Institute for Advanced Spinal Research. Last December the company received approval from the U.S. Food and Drug Administration (FDA) to initiate a study evaluating the M6-C artificial cervical disc with patients suffering from degenerative disc disease of the cervical spine; a common cause of neck and arm pain.

The M6 artificial disc represents the company's first non-fusion, motion preservation products to treat degenerative diseases of the spine. The M6 is an advanced generation artificial disc developed to replace an intervertebral disc damaged by cervical disc degeneration. It is the only artificial disc that replicates the anatomic structure of a natural disc by incorporating an artificial nucleus and annulus. Together, the artificial nucleus and annulus are designed to provide the same motion characteristics of a natural disc.

The M6's compressible polymer nucleus is designed to simulate the function of the native nucleus, while the surrounding multi-layer high tensile strength fiber annulus is intended to facilitate a controlled range of motion in multiple directions. The M6 artificial disc is implanted with proprietary surgical instrumentation. This specialized system was designed with surgeon feedback and is intended for simple, safe, and reproducible M6 implantation.

"We are extremely pleased with our recent FDA approval to move forward with the M6 feasibility trial, as well as completion of our first U.S. implantation by Dr. Lauryssen and his team at Olympia," says Tom Afzal, Spinal Kinetics President and CEO. "The M6 artificial cervical disc represents our initial commitment as an organization to provide both physicians and patients alike the most innovative motion preservation technologies for treating degenerative diseases of the spine."

Artificial disc technology provides an alternative to spinal fusion in the treatment of degenerative disc disease. Preserving motion with an artificial disc provides an opportunity to restore biomechanical function at the treated level after disc removal, as well as the possibility to reduce subsequent degeneration of adjacent segments.

"The M6 artificial disc represents the latest advancement in artificial disc technology with its unique structural and performance characteristics and its ease of use," states Carl Lauryssen, M.D., Chief of Spine Surgery at Olympia Medical Center in Beverly Hills, California. "As a physician, I am excited that this technology is now clinically available to patients, allowing us to conduct a strict and regimented study to prove the M6's clinical benefits."

Founded in 2003, Spinal Kinetics is a privately-held medical device company focused on partnering with spine surgeons to develop innovative and practical motion preservation systems for treating degenerative diseases of the spine. The company is located in Sunnyvale, California.