Abbott Announces Positive Results From Phase 2 Study Of Low Dose Atrasentan For Treatment Of Diabetic Kidney Disease

Main Category: Diabetes
Also Included In: Urology / Nephrology;??Clinical Trials / Drug Trials;??Pharma Industry / Biotech Industry
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Abbott (NYSE: ABT) announced positive results from a Phase 2 dose-ranging study of atrasentan, a highly selective endothelin A receptor antagonist in development to help slow chronic kidney disease (CKD) progression in patients with type 2 diabetic nephropathy (diabetic kidney disease). Study results suggest that atrasentan, used in conjunction with renin-angiotensin system (RAS) inhibitors, may reduce albuminuria (presence of protein in urine) for patients with type 2 diabetes. Albuminuria is the main sign of diabetic nephropathy and as kidney function decreases, the level of albumin in the urine rises. Results were presented at the annual American Society of Nephrology meeting in Denver, Colorado.

Key findings from the 8-week study of three doses of atrasentan (0.25 mg, n=22; 0.75 mg, n=22; 1.75 mg, n=22) vs. placebo were:

-- Atrasentan significantly reduced urine albumin-to-creatinine ratio (UACR) in the 0.75 mg and 1.75 mg groups vs. placebo (P=0.001 and P=0.011 by repeated measures, respectively). The 0.25 mg dose had no significant effect

-- Reduction from baseline to final UACR was 21%, 42%, and 34% in the 0.25 mg, 0.75 mg and 1.75 mg groups vs. 11% in placebo (P=0.292, P=0.023 and P=0.080, respectively)

-- A statistically significant proportion of subjects achieved >40% reduction in UACR from baseline in the 0.75 mg group vs. placebo (50% vs. 17% respectively, P=0.029). The proportion of patients in the 0.25 mg and 1.75 mg groups (30% and 38% respectively) did not reach statistical significance.

-- Peripheral edema (primarily mild) was the most common adverse event (14%, 18% and 46% for 0.25, 0.75 and 1.75 mg with p=0.007 for 1.75 mg vs. 9% in placebo)

"Several large clinical trials with RAS inhibitors have demonstrated that reductions in albuminuria are associated with a delay in the progression of diabetic nephropathy," said Donald E. Kohan, M.D., Ph.D., Professor of Medicine, Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah and lead investigator for the study. "These study results are encouraging and suggest that atrasentan may have an additional therapeutic role for albuminuria reduction on top of the current standard of care for patients with type 2 diabetes."

"The impact of chronic kidney disease is a growing global public health concern but few advancements in treatment have been made in the last decade that positively affect outcomes for patients with this progressive disease," said James Stolzenbach, Ph.D., divisional vice president, Dyslipidemia and Renal, Abbott. "Longer, outcome-driven clinical trials are needed to establish the safety and efficacy of atrasentan in diabetic nephropathy, but we are encouraged by the findings from this study and look forward to further evaluating atrasentan as a candidate for treating this type of chronic kidney disease."

Study Objectives and Design

The study was a double-blind, dose-ranging, placebo-controlled study of 89 subjects with diabetic nephropathy on stable doses of renin-angiotensin system (RAS) inhibitors for >2 months with urinary albumin-to-creatinine ratio (UACR) of 100-3000 mg/g, eGFR >20 mL/min/1.73m squared, and NT-pro-BNP <500 pg/mL. Patients were equally randomized to placebo, atrasentan 0.25, 0.75, or 1.75 mg daily for eight weeks. The study's primary endpoint was mean change in UACR ratio from baseline to each treatment visit. The secondary endpoint was measured as the proportion of subjects achieving at least a 40 percent reduction in final UACR levels from baseline.

About Atrasentan

Atrasentan is an investigational compound belonging to a class of compounds known as selective endothelin-A receptor antagonists, which block the effect of endothelin-l (ET-l), a protein that constricts blood vessels and raises blood pressure that impact kidney functions. Atrasentan is a highly selective endothelin-A receptor antagonist that shows promise in targeting the effect of endothelin in diabetic nephropathy. Atrasentan was discovered and developed by Abbott scientists.

About Chronic Kidney Disease (CKD) and Diabetic Nephropathy

CKD is a highly prevalent condition worldwide, with numbers expected to rise over the next decade. CKD is often under diagnosed due to a lack of symptoms in early stages. Data from the U.S. Renal Data System (USRDS) suggest there has been a 30 percent increase in chronic kidney disease in the United States over the past decade. CKD affects an estimated 26 million Americans. In addition, half of CKD patients also have diabetes, a percentage that is expected to grow as rates of diabetes increase. Diabetic CKD patients account for approximately 24 percent of total Medicare diabetes costs. Current treatments modestly slow the progression of CKD, and patients ultimately progress to dialysis and end-stage disease.

Source: Abbott

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CellerateRX® Effectively Manages Diabetic Ulcers, New CDC Report Indicates Type 2 Diabetes On The Rise

Main Category: Diabetes
Also Included In: Dermatology
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Wound Management Technologies, Inc., (OTC Bulletin Board: WNDM) a leader in advanced wound care solutions, is meeting the challenge of a rise in type 2 diabetes in the US, as chronicled by a new report by the Center for Disease Control (CDC). The report published in the October 22, 2010 journal Population Health Metrics recommends that proper diet and physical activity can prevent type 2 diabetes and reduce its complications, among the most severe of which are diabetic ulcers and amputations. Wound Management, exclusive worldwide licensee and distributor of CellerateRX® wound care powder and gel, further recommends that existing diabetic patients who suffer from moderate to heavily exudative wounds should ask their doctor whether CellerateRX® may be an effective treatment for them. CellerateRX® is the only activated Type 1 collagen-based product reimbursed by Medicare and has been shown to effectively manage diabetic ulcers.

Diabetes is $174B Cost to US Economy

The current CDC report states that the total costs of diabetes are currently estimated to be $174 billion annually, including $116 billion in direct medical costs. If CDC recommendations are not widely adopted and current trends of obesity continue, diabetes is projected to affect between 1 in 3 to 1 in 5 Americans by 2050.

Untreated Diabetic Wounds Can Lead to Amputations

Diabetics are at high-risk for wound infection due to their varying blood sugar levels, circulation changes, and impaired local immune defenses, all of which predispose them to delayed healing and infection. Diabetic wound complications are the most common cause of non-traumatic lower extremity amputations in the industrialized world. According to the Centers for Disease Control (CDC), sixty percent of lower limb amputations are associated with diabetes. "Between 15-25% of people with diabetes will develop foot and leg ulcers at some point (1) in their lives," said Cathy Bradshaw, President of Wound Care Innovations, LLC.

CellerateRX® Effectively Manages Diabetic Ulcers

Wound Care Innovations' advanced wound care collagen product, CellerateRX®, has been shown in multiple clinical applications and settings to be extremely effective in managing these challenging diabetic wounds. In one study, wounds where CellerateRX® was applied were healed within five (5) weeks with a once or twice per week application. This is in contrast to the control wounds that were only approximately 80% healed at twelve (12) weeks.(2) "The ideal product to effectively manage these difficult wounds provides for quality outcomes in a cost effective manner," said Dr. Larry Baratta, VP of Medical Affairs. "CellerateRX® has been shown to do just this." Jane Fore MD, FAPWCA, FACCWS, Medical Director, Tri-State Wound Care and Hyperbaric Center states, "CellerateRX is the standard of care in my clinic. This product is compatible with other wound care products and gives the wound environment the basic building blocks for growth, and contributes an essential part of the wound matrix that supports the migration of cells to healing tissues. Wound healing deficiencies are more common in diabetics and CellerateRX® collagen provides an essential factor that aids in overcoming challenges in healing diabetic wounds."

CellerateRX® Activated Collagen is the Differentiator

CellerateRX's activated collagen (approximately 1/100th the size of native collagen) delivers the essential benefits of collagen to a wound immediately, where other forms of native, intact collagen in commercially available products require time for the body to prepare the collagen for use in the wound healing process. In people with compromised health or circulation, the difference in wound healing can be significant.

CellerateRX® is FDA cleared for all wound types except for 3rd degree burns and is available in both powder and gel form. In addition to being used in healthcare settings throughout the country, CellerateRX® is easily applied by patients by themselves at home.

Safe Harbor Statement:

The statements in the press release that relate to the company's expectations with regard to the future impact on the company's results from new products in development and any other statements not constituting historical facts are "forward-looking statements," within the meaning of and subject to the safe harbor created by the Private Securities Litigation Reform Act of 1995. Since this information may contain statements that involve risk and uncertainties and are subject to change at any time, the company's actual results may differ materially from expected results. This document may contain forward-looking statements concerning the Company's operations, current and future performance and financial condition. These items involve risks, contingencies and uncertainties such as product demand, market and customer acceptance, the effect of economic conditions, competition, pricing, the ability to consummate and integrate acquisitions, and other risks, contingencies and uncertainties detailed in the Company's SEC filings, which could cause the company's actual operating results, performance or business plans or prospects to differ materially from those expressed in, or implied by these statements. The Company undertakes no obligation to revise any of these statements to reflect the future circumstances or the occurrence of unanticipated events.

References

(1) Archive for the "Diabetic Skin Ulcers," April 2010

(2) "Activated Collagen: An Evidence Based Study in Human Leg Ulcers," Dr. Regulski, SAWC 2009

Source: Wound Management Technologies, Inc.

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Potential drug therapy for diabetic retinopathy under study

ScienceDaily (Nov. 8, 2010) ? One drug's startling ability to restore retinal health in the eyes of diabetic mice has researchers wanting to learn more about how it works and whether it might do the same for people.

"We want to know if this drug has the potential to block the visual devastation that can occur with diabetes," said Dr. Sylvia Smith, retinal cell biologist and co-director of the Vision Discovery Institute at the Medical College of Georgia. "That means we need to know more about how and when it is effective."

Diabetic retinopathy, the leading cause of blindness in working-age Americans, results from the destruction of the retina, a thin layer at the back of the eyeball that converts lights to signals that the brain can interpret as images. The retina, which deals with daily assaults from the sun and other external forces, is slowly injured by the high glucose levels of diabetes then further injured when it grows more blood vessels in an attempt to get more blood and oxygen to dying cells.

At least in the early stage of diabetes in mice, MCG researchers appear to have interrupted the first wave of cell destruction with the drug (+)- pentazocine -- known for its pain-relieving power -- by reducing cell stress. A new $1.5 million grant from the National Eye Institute will enable scientists to test their cell stress theory and fill in missing pieces about how and when the drug works.

Smith and her colleagues have evidence that oxidative stress, believed to be a key player in the cell damage resulting from diabetes, increases the binding of sigma receptors to BiP, a stress protein. Sigma receptors are believed to help cells cope with stress.

While some results of the union are unclear, it is clear that in the mice, (+)- pentazocine reduces binding between the two to a more usual, non-stressed level and restores the typically well-stratified retina to a more healthy state. Smith termed the result "phenomenal" when it was published in Investigative Ophthalmology & Visual Science in 2008. In fact, subsequent research has shown, (+)- pentazocine improves the look of the multi-layer retina in a healthy mouse.

"We know (+)- pentazocine binds to sigma receptors, but one of the things we don't know is if the binding blocks or promotes sigma receptor action," Smith said. Working with Dr. Eric Zorilla at The Scripps Research Institute in California, Smith now has mice with sigma receptors deleted that will help her better determine their role and how (+)- pentazocine intervenes.

Dr. Alan Saul, MCG electrophysiologist skilled in measuring the response of the retina to light, is helping her objectively measure the impact on mouse vision. Much like an EEG measures the electrical activity of the brain, Saul, a faculty member in the MCG Department of Ophthalmology, helps measure the electrical response of the retina -- which is part of the brain -- to light as an objective vision test to accompany the more common vision chart.

Without a mouse vision chart, it's hard to be certain that a better-looking retina translates to better vision, Smith said. In fact, Saul has seen it go both ways in patients: an eye exam indicates good vision while the retinal test shows differently, and vice versa. "You are surprised a lot of the time," Saul said. In fact, they are beginning to find some surprises in mice with a related problem. Diabetes essentially doubles the glaucoma risk and as their mice with glaucoma reach the equivalent of their 20s and 30s in human years. Saul's electrical exams show early changes in their optic nerves -- which extend from the retina to the brain -- even though they look normal on microscopic exam.

To help fill in the knowledge gaps, the scientists are inducing diabetes in the mice missing sigma receptors, comparing them to healthy mice and applying non-diabetic stressors to the sigma receptor knockouts. They suspect that other stressors, including age, also cause retinal damage.

Goals include determining if retinal appearance improves as a result of the interaction between the sigma receptors and (+)- pentazocine and consequent reduction of cell stress. To help explore the therapeutic potential, they also want to see whether the drug is effective if given later in the disease process. In their earlier studies, the drug was given immediately after mice became diabetic, an unlikely stage of diagnosis for most human diabetics.

"If we can get answers to these questions we'll know better whether (+)- pentazocine has the potential to help patients, which is our ultimate goal," Smith said.

To help prevent progression of diabetic retinopathy, patients are encouraged to control glucose and cholesterol levels as well as blood pressure. Laser treatment can help destroy excessive blood vessels that hinder vision and reduce swelling often associated with the condition.

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Medical College of Georgia. The original article was written by Toni Baker.

Note: If no author is given, the source is cited instead.

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Diabetic Adults' Conditions Improved After Phone Calls With Fellow Patients

Main Category: Diabetes
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Phone calls with a peer facing the same self-management challenges helped diabetes patients manage their conditions and improved their blood sugar levels better than those who used traditional nurse care management services alone, according to research from the University of Michigan Health System.

The findings, published Oct. 19 in the Annals of Internal Medicine, showed the peer partner program resulted in lower glycated hemoglobin (HbA1c) levels after six months among men with uncontrolled diabetes.

The research was based on a peer partnership program established by the Veterans Affairs Ann Arbor Health System and the University of Michigan Medical School.

Each peer pair received initial brief training in peer communication skills and was expected to communicate by telephone at least once a week about their mutual efforts to improve diabetes control. Program participants also were offered optional periodic nurse-facilitated group sessions to exchange experiences with fellow patients.

"Our model was testing the hypothesis that a good way to activate patients was to give them some skills and encouragement to both help and be helped. Just as in education they say that the best way to learn something is to try to teach it," says study lead author Michele Heisler, M.D., who is a research scientist for the Center for Clinical Management Research at the VA Ann Arbor's Health Services Research & Development Center of Excellence and associate professor of internal medicine at the U-M's Medical School. Heisler also is associate professor of health behavior and health education at U-M's School of Public Health.

"We are trying to tap into the underappreciated expertise of patients," Heisler says. "Most disease management programs put patients in the 'learner' role, whether nurse care management programs or 'expert' peer programs. But patients know a lot about living with their condition and strategies they have developed so have a lot to share with others also struggling. Our program hoped to mobilize patients themselves to realize how much they themselves had to offer another person with diabetes and enjoy the sense of meaning and pleasure that being needed and helping another can provide.

That's why I think people did well-- they were very motivated when they felt they were helping someone else."

In the peer support group, researchers randomly assigned 244 VA patients with uncontrolled diabetes to either peer support or traditional nurse care management. At the start, patients in the peer support group met in a group setting to set their own disease management goals and specific steps they wanted to take over the next few weeks, received basic peer communication tips, were matched with another study participant of similar age (their peer partner), and were advised to talk with their peer partner once per week. For their peer calls they used the telephones but through a system that linked calls without their having to exchange their telephone calls, that enabled them to block calls at certain hours, and that provided reminder calls if they missed a week.

Heisler says she and her fellow researchers expected to see benefits from the peer support, but were surprised at how large the improvement in glycemic control from the program after six months was. The patients who were randomly assigned to the peer support program achieved HbA1c levels that were 0.58 percentage points lower on average than those in the nurse care management group. And patients in the peer support group with baseline HbA1c levels greater than 8 percent achieved a mean decrease of 0.88 percentage points, compared with a 0.07-percentage point decrease among those in the nurse care management group. This is equivalent to that achieved by starting another oral anti-hyperglyemic medication.

More patients in the peer support group also started insulin therapy at much higher rates than those in the nurse care management group, a step that many patients resist.

"The higher rate of insulin therapy initiation in the peer support group suggests that patents' concerns about insulin may be best addressed by another person who also is coping with insulin management," Heisler says.

Heisler says this is the first randomized controlled trial to examine reciprocal peer support in chronic disease management. This can be a low-cost, easy-to-implement system that allows patients to get more one-on-one support in managing a chronic illness, Heisler says.

"Most chronically ill patients need more support for self-care than most health care systems can provide. That's why programs like this, that increase the quality and intensity of assistance through peer support, deserve further exploration," Heisler says.

Additional authors: Sandeep Vijan, M.D., of U-M and VA Ann Arbor; Fatima Makki, M.P.H, M.S.W. of VA Ann Arbor; John Piette, Ph.D., of U-M and VA Ann Arbor.

Funding: U.S. Department of Veterans Affairs Health Services Research and Development Service (HSR&D)

Source:
University of Michigan Health System

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posted by Louis Brinn on 21 Oct 2010 at 12:45 pm

This study is really innovative. They used people instead of mice with cell phones. They as usual did not announce a cure or a med that would permit normal life as usual. Who ever funded this study is to be commended for this. Not only did they not discover a cure or effective meds but they made the people involved feel good about themselves and not resist the same old insulin that has been around for so many years.
I bet they did not even tell direct relatives that they might be up for a lot of phone calling and insulin real soon. Hurrah for modern medicine.

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Chromium picolinate may lessen inflammation in diabetic nephropathy; Supplement linked to decreased protein in the urine of diabetic mice

ScienceDaily (Sep. 22, 2010) ? Taking chromium picolinate may help lessen inflammation associated with diabetic nephropathy (kidney disease), say researchers at the Medical College of Georgia in Augusta. In a study comparing diabetic mice treated with chromium picolinate with those that received placebo, the researchers found that mice who received the supplement had lower levels of albuminuria (protein in the urine), an indication of kidney disease.

To arrive at their conclusions, the researchers compared three groups of mice, one lean, healthy group and two groups genetically engineered to be obese and have diabetes. When the mice were 6 weeks old, the researchers separated them according to treatment plan. The healthy mice and one group of diabetic mice, the untreated diabetic group, were fed a regular rodent diet. The remaining group, the treated diabetic group, were fed a diet enriched with chromium picolinate.

Over the course of 6 months, the researchers measured glycemic control and albuminuria in all three groups. The untreated diabetic mice excreted nearly 10 times more albumin than the db/m mice, which was to be expected. However, the treated diabetic mice, who were fed the diet with chromium picolinate, excreted about half as much albumin compared to their untreated diabetic counterparts.

At the end of 6 months, the mice were euthanized and the researchers studied tissue samples from the mice's kidneys. They found that the untreated diabetic mice had marked immunostaining for interleukin 6 (IL-6) and interleukin 17 (IL-17), two cytokines associated with inflammation. These mice also had moderate immunostaining for indolamine 2,3-dioxygenase (IDO), an immunoregulatory enzyme that modulates the production of IL-6 and IL-17. However, the treated diabetic mice had intense immunostaining for IDO but reduced IL-6 and IL-17 compared to the untreated diabetic group. The implication is that the chromium picolinate may have reduced inflammation in the treated diabetic group by affecting IDO, IL-6, and IL-7.

Mahmood Mozaffari, DMD, PhD, professor in the Medical College of Georgia Department of Oral Biology and lead author of the study, noted that the results are preliminary and that further studies are necessary to tease out the effects of chromium picolinate. He is particularly interested in the relationship between IDO and chromium picolinate because IDO is involved in the metabolism of tryptophan, an amino acid, and one of the by-products of that metabolism is picolinic acid.

"This clearly raises an important question for us as to whether our observations are related to the provision of picolinic acid from the chromium picolinate or whether the formulation [chromium picolinate], in and of itself, is mediating the effects."

Dr. Mozaffari discussed the study at the 2010 American Physiological Society conference, Inflammation, Immunity, and Cardiovascular Disease, in Westminster Colorado.

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by American Physiological Society.

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