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Saturday, September 25, 2010

Improving Clinical Trials Act passes!

I know many of you wrote to your Congress people over the past year and I want to THANK YOU for your efforts.

WE HAVE BEEN SUCCESSFUL! This new bill will translate into more CFers participating in clinical trials for life-changing drugs for CF.


"Improving Clinical Trials Act" Passes House and Senate, Heads to President for Signature

Sept 23, 2010

Today the U.S. House of Representatives passed the “Improving Access to Clinical Trials Act” (I-ACT), in a victory for the Cystic Fibrosis Foundation, its advocates and 120 other health advocacy organizations.

The bill, which passed the Senate Aug. 5, now goes to President Obama’s desk for his signature. He is expected to sign it.

This legislation enables patients with rare diseases to participate in clinical trials without losing eligibility for public healthcare benefits. Passage of this legislation is particularly important for people with CF, a rare genetic disease.

A limited patient population makes it challenging to find enough people to participate in research studies evaluating the effectiveness of promising new drugs.

“Because of this groundbreaking legislation, people with CF and other rare diseases will no longer be forced to choose between critical health care coverage and participation in research that could lead to the development of a cure for our most serious illnesses,” said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation.

“We are grateful to our champions in Congress for approving this bill, which will help move new treatments more swiftly from the lab to the patients who need them most.”

Cystic Fibrosis Caucus Co-Chairs, Reps. Edward Markey, D-Mass., and Cliff Stearns, R-Fla., led the effort to pass the bill in the House. The House version of this legislation, HR 2866, has 141 co-sponsors.

"No one should have to choose between participating in a clinical trial and accessing the essential benefits they need. Today's bill will open doors of hope and offer the possibility of better health to those with rare diseases like cystic fibrosis. I am proud to partner with my friend and co-chairman of the Congressional Cystic Fibrosis Caucus, Congressman Cliff Stearns, in the passage of this bi-partisan bill, which now will be signed into law by President Obama. I also want to commend the Cystic Fibrosis Foundation for its incredible work on this vital issue. Today represents an important and hopeful milestone in the battle to beat devastating rare diseases that afflict millions of Americans around the country," Markey said.

Added Stearns: "As co-chair and co-founder of the Congressional Cystic Fibrosis Caucus, I commend my colleagues for approving this legislation allowing people with rare diseases such as cystic fibrosis to participate in life-saving clinical trials that provide nominal compensation without the risk of losing their health care coverage. I also deeply appreciate the work of the Cystic Fibrosis Foundation in supporting my legislation."

The Senate version of the legislation, S. 1674, was introduced by Sen. Ron Wyden, D-Ore., with Sens. Chris Dodd, D-Conn., James Inhofe, R-Okla., Richard Shelby, R-Ala., and Dick Durbin, D-Ill., as original co-sponsors. An additional 17 co-sponsors signed on.

Current law prevents many people who receive Supplemental Security Income (SSI) from accepting research compensation because it makes them ineligible to receive government medical benefits. This penalty has stopped significant numbers of people with rare diseases from participating in clinical studies.

EU approval rec for TIP

Novartis International AG: Novartis receives EU approval recommendation for TOBI® Podhaler®, a fast and simple therapy that helps reduce treatment burden for cystic fibrosis patients

Fri Sep 24, 2010 9:17am EDT

Novartis International AG / Novartis receives EU approval recommendation for TOBI

Podhaler, a fast and simple therapy that helps reduce treatment burden for cystic fibrosis patients processed and transmitted by Hugin AS. The issuer is solely responsible for the content of this announcement.

CHMP supports approval of TOBI Podhaler, a new dry powder form of tobramycin for treating chronic P. aeruginosa lung infection in cystic fibrosis patients over six

Data show new formulation reduces administration time by 72% compared to TOBI, with same

efficacy[1] and using more convenient, patient-friendly device


Cystic fibrosis is a life-threatening genetic disease primarily affecting children and young adults - complex daily treatment reduces their ability to lead normal lives

Basel, September 24, 2010 - TOBI® Podhaler® (tobramycin inhalation powder), a fast and

convenient inhaled therapy[1] for use by patients with cystic fibrosis (CF), has been

recommended for approval in the European Union. The Committee for Medicinal Products for

Human Use (CHMP), which reviews medicines for the European Commission, issued a positive

opinion for TOBI Podhaler as a suppressive therapy for chronic Pseudomonas aeruginosa

(Pa) infections in CF patients aged six years and older.

"TOBI Podhaler combines a number of innovations that significantly improve the delivery

of tobramycin, which is an established effective treatment for Pa lung infection in

patients with cystic fibrosis," said Professor Stuart Elborn, Professor of Respiratory

Medicine at Queens' University, Belfast, and President of the European Cystic Fibrosis

Society. "This therapy should help patients to lead more independent lives - an

important factor considering the relatively young age of many people with this disease."

The CHMP based its positive opinion on data showing that TOBI Podhaler provides the same

efficacy[2] as TOBI® (tobramycin solution) with a comparable safety profile[2]. TOBI is

the most widely used inhaled antibiotic for chronic Pa infections in CF[3]. TOBI

Podhaler has a unique dry powder formulation, developed using novel PulmoSphere®

technology to produce particles that are light and porous for deep delivery into the

lung. This means treatment can be given with a portable, patient-friendly device, in

contrast to TOBI which is administered with a nebulizer.

Data show that patients using TOBI Podhaler completed their tobramycin treatment in five

to six minutes instead of 20 minutes with TOBI, a reduction of 72%[1]. Nebulized

treatments require additional time for assembly and disinfection, unlike TOBI Podhaler,

which also does away with the need for refrigeration of the active compound and a power

source for the delivery device. A study found that patients treated with TOBI Podhaler

had significantly higher treatment satisfaction than those treated with TOBI[1].

Due to the complexity of existing anti-Pa treatment, most patients do not fully adhere

to their therapy[4],[5],[6]. In addition, many patients do not clean their nebulizers

properly and these are often contaminated[7],[8],[9],[10]. With TOBI Podhaler, the

inhaler device is disposable and the dry formulation potentially reduces the risk of

bacterial contamination.

"TOBI Podhaler shows how we are applying innovative technologies to better meet the

needs of patients and their families," said David Epstein, Division Head of Novartis

Pharmaceuticals. "TOBI Podhaler also underscores our long-term commitment to improving

the quality of care for patients with diseases such as cystic fibrosis and helping them

to lead longer and more active lives."

Cystic fibrosis (CF) is a life-threatening genetic disease that affects the internal

organs, especially the lungs and digestive system, by clogging them with thick mucus

making it hard to breathe and digest food. A total of 70,000 patients have been

diagnosed with CF worldwide[11]. Symptoms usually develop within the first year of life

and only half of CF patients live to over 35 years of age[12]. In 90% of cases, death is

due to a progressive decline in lung function often made worse by chronic Pseudomonas

aeruginosa infection[13].

The first launch of TOBI came in 1997 and it is now approved in 46 countries including

the US and EU for the treatment of Pseudomonas aeruginosa in CF patients aged six years

old and above.

TOBI Podhaler was submitted for EU approval in December 2009 and is not yet approved in

any country. The European Commission generally follows the recommendations of the CHMP

and is expected to make a decision within three months.

Wednesday, September 22, 2010

$25 for a quick survey

If you're a CF adult, you may qualify for $25 to participate in a quick online survey.

Please mention you heard about this from the NoExcuses blog.

please contact us at CF_Panel@WWMR.com call  888-947-2339, choosing option 3 at the main menu

Sunday, September 12, 2010

Effects of exercise on respiratory flow and sputum properties in cystic fibrosis.

Chest. 2010 Sep 9.

Effects of exercise on respiratory flow and sputum properties in cystic fibrosis.

Dwyer TJ, Alison JA, McKeough ZJ, Daviskas E, Bye PT.
1Discipline of Physiotherapy, Faculty of Health Sciences, University of Sydney, Sydney, Australia.

BACKGROUND: The physiological mechanisms by which exercise may clear secretions in subjects with cystic fibrosis (CF) are unknown. The purpose of this study was to compare ventilation, respiratory flow and sputum properties following treadmill and cycle exercise to resting breathing (control).

METHODS: In 14 adult subjects with CF, ventilation and respiratory flow were measured during 20 minutes of resting breathing, treadmill and cycle exercise in a three-day, cross-over study. Treadmill and cycle exercise were performed at the workrate equivalent to 60% of the subject's peak VO(2). Ease of expectoration and sputum properties (solids content and mechanical impedance) were measured before and immediately after the interventions and after 20 minutes recovery.
RESULTS: Ease of expectoration improved following exercise. Ventilation and respiratory flow were significantly higher during treadmill and cycle exercise, compared to control. Sputum solids content did not change following treadmill or cycle exercise. There was a significantly greater decrease in sputum mechanical impedance following treadmill exercise compared to control, but no significant decrease in sputum mechanical impedance following cycle exercise compared to control.
CONCLUSIONS: The improvement in ease of expectoration following exercise may have been due to the higher ventilation and respiratory flow. The reductions in sputum mechanical impedance with treadmill exercise may have been due to the trunk oscillations associated with walking.

Friday, September 3, 2010

Mutational spectrum of cystic fibrosis in the Lebanese population

J Cyst Fibros. 2010 Aug 25. [Epub ahead of print]

Mutational spectrum of cystic fibrosis in the Lebanese population.

Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Department of Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Genetics Laboratory, Chronic Care Center, Hazmieh, Lebanon.


BACKGROUND: Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians; it is however, considered to be rare in the Arab populations. Reports of the cystic fibrosis transmembrane regulator (CFTR) mutations from Arabs, especially from the Lebanese population, are limited.

METHODS: Twenty-two unrelated Lebanese families, with at least one child with CF, were studied. DNA extracts from blood samples of patients and parents were screened for CFTR gene mutations.
RESULTS: Eleven different mutations were identified. Of the 44 alleles studied, the most common mutations were: F508del (34%), N1303K (27%), W1282X (7%), and S4X (7%). Five mutations - not previously reported in the Lebanese population - were identified; these are: S549N, G542X, 2043delG, 4016insG, and R117H-7T.

CONCLUSIONS: The most common CFTR mutations in addition to five mutations not previously described in the Lebanese population were identified. Identification of CFTR mutations in the Lebanese population is important for molecular investigations and genetic counseling.

NIH Awards $1.2 Million To Study Protein Misfolding Diseases

NIH Awards $1.2 Million To Study Protein Misfolding Diseases

Three University of Massachusetts Amherst scientists have received a four-year, $1.2 million EUREKA grant from the U.S. National Institutes of Health (NIH) to study folding and misfolding of secretory proteins in the cell's protein factory, the endoplasmic reticulum, where misfolding can lead to diseases such as cystic fibrosis and liver cirrhosis.

EUREKA stands for Exceptional, Unconventional Research Enabling Knowledge Acceleration. The program was created by NIH's National Institute for General Medical Sciences to support scientists who are testing new ideas in unusual ways or tackling major methodological or technical challenges. Janna Wehrle, who manages this and other protein folding grants at NIH, says, "This project represents an exceptionally bold effort to determine how proteins fold not in a test tube but in real cells. By examining how proteins take shape in the crowded and dynamic environment where it actually occurs, this work may lead to a better understanding of how the folding process goes awry in diseases like cystic fibrosis and some forms of liver cirrhosis."

Anne Gershenson and her biochemistry and molecular biology colleagues Daniel Hebert and Lila Gierasch begin pilot studies this month using new techniques they adapted to observe how individual secretory proteins fold, not only in real cells but in real time. For this work, they will also use a powerful new super-resolution fluorescence microscope built by UMass Amherst physicist Jennifer Ross and her students. It provides a clear view of individual molecules with far more precision than was possible using traditional light microscopy.

Members of this UMass Amherst research group have been pioneers in studying proteins in situ, or in place, rather than in test tubes. Up to now, much valuable protein-folding research has used whole purified proteins that are forced by heating or other treatment to unfold in a test tube. Scientists then study their refolding into the three-dimensional shapes necessary to carry out the cell's tasks. But as Gershenson and Gierasch pointed out in an influential 2009 article in Nature Chemical Biology, "we have arrived at the post-reductionist era of biochemistry" when it is no longer enough to study isolated parts of complex networks. Rather, they say scientists must now examine proteins in their native, complicated and highly concentrated environments to truly understand the way they work.

The cell's endoplasmic reticulum is a protein-folding factory, churning out hundreds of secretory proteins to be exported from cells, as well as membrane proteins that reside on the cell surface, Gershenson explains. This factory comes complete with a large number of proteins responsible for quality control. They assist in folding and determine whether and when a protein should be exported to take up its required position. How proteins fold as they are synthesized and how quality control mechanisms affect protein folding are the focus of Gershenson and colleagues' investigation.

The UMass Amherst researchers use a technique called fluorescence resonance energy transfer, or FRET, for light-marking proteins and monitoring their folding. In it, two differently-colored fluorescent dyes that are sensitive to each other, a donor and an acceptor, are introduced into the protein chain as it is made. When these are farther apart in a not-yet-folded protein, the donor emits greener fluorescence. As the protein folds and the two dyes get closer together on the three-dimensional structure, their proximity results in emission of a redder fluorescence. Spectroscopically analyzing the fluorescence allows investigators to precisely track donor-to-acceptor distance changes.

Further, by introducing the FRET donor and acceptor molecules at slightly different parts of the protein chains in each of hundreds of experiments, Gershenson and colleagues will be able to map protein changes associated with folding in situ, in real time.

"Once we get the system operating with good fluorescence and we become adept at incorporating the FRET dyes, our method should prove useful to other researchers for studying a wide variety of other proteins which are involved in many other disease processes," she says. "That's the big promise of this approach, and the challenge."

Over the three years of the program, NIH has awarded 56 grants totaling $67.4 million to support these highly innovative research projects which promise big scientific payoffs. Awards announced today total $25.2 million to 21 institutions.

Source: University of Massachusetts Amherst

Viagra Trial in Children and Young Adults With CF

Sildenafil Trial in Children and Young Adults With CF
This study is not yet open for participant recruitment.
Verified by Children's Hospital Medical Center, Cincinnati, September 2010
First Received: September 1, 2010   No Changes Posted
Sponsor: Children's Hospital Medical Center, Cincinnati
Information provided by: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01194232
Cystic Fibrosis (CF), the most common inherited disease in Caucasians, is characterized by chronic pulmonary inflammation and progressive loss of gas exchange units that eventually results in respiratory failure. There is strong evidence that, in CF, abnormally low perfusion carries a high risk of death independent from the presence of pulmonary hypertension. However, the evolution of pulmonary vascular disease in CF and how it might contribute to the rate of decline in lung function is not known. Our knowledge remains limited to the results of old observational studies which concluded that the major causes of pulmonary vascular remodeling and hypertension in CF are hypoxic respiratory failure and destruction of lung tissue. Our recent data obtained by state-of-the-art Magnetic Resonance Imaging (MRI) of the pulmonary circulation, challenges the existing paradigm. We demonstrate that in the absence of hypoxia, significant changes in pulmonary perfusion and in surrogate measures of vascular resistance as well as in collateral blood flow begin early in the course of CF. Newly developed therapeutics have altered dramatically the course of patients suffering from pulmonary vascular disease. Through this 8 week trial, we will examine by Magnetic Resonance Imaging the effect of Sildenafil on pulmonary perfusion and systemic vascularization of the lungs in subjects with mild to moderate disease.

Condition Intervention Phase
Cystic Fibrosis With Mild to Moderate Lung Disease
CMRI of Lung Perfusion
Lung Perfusion
Lung Vascularization
Drug: Sildenafil
Phase I
Phase II

Study Type: Interventional
Study Design: Allocation: Randomized
Control: Uncontrolled
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Controlled Study of Sildenafil in Children and Young Adults With Mild to Moderate Cystic Fibrosis Lung Disease

Resource links provided by NLM:

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Increase pulmonary perfusion [ Time Frame: 8 week visit ] [ Designated as safety issue: No ]
    • Increase of pulmonary perfusion by a minimum of 15% as measured by gadolinium contrast MRI with segmental perfusion and scored on a continuous scale;

Secondary Outcome Measures:
  • Improved lung function [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    • Improved exercise performance as measured by the following variables:
    • Ventilatory equivalent of O2 and CO2 (VEO2 and VECO2)
    • Maximum oxygen consumption (VO2 max)

Estimated Enrollment: 36
Study Start Date: October 2010
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sildenafil: Experimental
24 subjects will receeive 8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose.
Drug: Sildenafil
8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose.


Ages Eligible for Study:   8 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
  • Age 8 years to age 21 years
  • Diagnosis of cystic fibrosis confirmed by a prior sweat chloride evaluation of > 60 mmol/liter or by two identified CFTR mutations on genetic analysis
  • Able to perform acceptable and repeatable spirometry per American Thoracic Society/European Respiratory Society (ATS/ERS) joint consensus criteria.
  • Have valid spirometry data for at least 3 years
  • Must have mild to moderate lung disease (Mild lung disease will be defined as an FEV1%p of 80-99% predicted. Moderate lung disease will be defined as an FEV1%p of 60-79% predicted.)
  • If under the age of 18, the subject must assent to participation in the study, and the subject's parent or guardian must be able to give written informed consent and comply with the requirements of the study protocol
  • If 18 years of age or older, the subject must be able to give written parental permission and comply with the requirements of the study protocol
  • For female subjects: negative serum pregnancy test and must be willing to use contraception during study participation
  • Able to tolerate MRI without sedation
  • Subjects who are on alternating monthly on/off cycles of inhaled antibiotics must be willing to be off of inhaled antibiotic therapy for one "on" cycle.
  • Must be currently enrolled in CCHMC IRB#: 2008-0926 5.2 Exclusion Criteria
Research subjects will be excluded from the study based on:
  • History of CF-related liver disease with portal hypertension
  • Currently smoking cigarettes or other tobacco products
  • Use of daytime oxygen supplementation
  • Previous organ transplantation
  • Unstable or uncontrolled hypertension
  • Ongoing use of oral corticosteroids
  • For female subjects: pregnancy or lactation and unwillingness to use contraception during study participation
  • Any hemodynamically significant congenital or acquired cardiac disease or significant cardiomyopathy, hematologic disease (i.e. hemoglobinopathies), or pulmonary disease associated with an increased risk of pulmonary perfusion defects or pulmonary hypertension other than as an outcome of CF
  • History of renal and/or hepatic insufficiency, defined as cystatin-C level that exceeds normal range and a previous diagnosis of liver cirrhosis.
  • History of uncontrolled asthma defined as oral steroid dependent
  • History of hypersensitivity to gadolinium (Magnevist)
  • Contraindications specific to MRI including a history of claustrophobia, cardiac pacemaker, or other non-MRI compatible surgical implants (This includes neuro-stimulators containing electrical circuitry, or which generate electrical signals and/or have moving metal parts, and metal orthopedic pins or plates. The research coordinator and/or the MRI technologist will screen all subjects using the standard checklist of medical history and safety questions used by the Radiology Department in routine clinical scans.)
  • Daily use of montelukast and ibuprofen
  • Use of nitrate medicines or other drugs known to have unsafe interactions with Sildenafil
  • Known allergy to Sildenafil
  • Inability to comply with study procedures
Laboratory Exclusion Criteria for research subjects (based on history or bloodwork before first MRI):
  • Positive sputum, epiglottic, or brochoalveolar lavage culture for Mycobacterium abscessus during the 2 years prior to enrollment
  • A positive serum pregnancy test
  • Serum creatinine > two times the upper limit of normal for age
  • A serum Cystatin C outside of normal range for age
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01194232

Contact: Lorrie Duan, RN 513-636-7089 lorrie.duan@cchmc.org
Contact: Margo Moore, RN 60394 margo.moore@cchmc.org

United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229

Thursday, September 2, 2010

Please vote for CF Pepsi Refresh Project

We are currently #2!

Let's vote once per day to help win $250,000 to fight CF.

Please share with friends and family.