FDA: Put Patients on Strict Diets in Trials for Metabolic Disorders

July 30, 2018

Sponsors studying genetic metabolic disorders should put patients on strict diets before clinical trials begin, the FDA says in a new draft guidance. Researchers have already developed drug treatments to complement the diets of people who suffer from such metabolic disorders as phenylketonuria, organic acidemia and urea cycle defects. But even small nutritional changes can affect clinical trial results, especially when a proposed drug’s impact is “relatively modest,” the FDA says. To address those challenges, the FDA recommends that participants in clinical trials be put on strict eating plans (that are clearly detailed) before studies start. While monitoring diets, sponsors should remember that the two most common assessments — food frequency questionnaires and food diaries — have limited value because they rely on “crude measures” and participant memory. The length of time participants spend on their pretrial diet should be based on their age, disorder (and its severity) and how complex the diet is, the guidance states. Patients with metabolic disorders often have to undergo surgeries, which, in turn, may require they go on specialized diets. Any surgeries should be completed well before a trial begins, the FDA says. The agency also discourages switchover trials in which patients are initially put on a special diet and then given a drug. “Without a concurrent control arm and blinding, switchover designs are unlikely to produce interpretable results,” the FDA says.Read the full guidance here:

Strict Blood Pressure Control May Reduce Dementia Risk
Aggressively controlling high blood pressure not only helps prevent heart problems, it may also help cut the risk of cognitive decline, according to new research. Wake Forest scientists found that participants at high risk of heart attacks and strokes who were treated to reduce their systolic blood pressure to a max of 120 instead of 140 were 19 percent less likely to suffer mild cognitive impairment, which can lead to dementia. In a second trial, a University of Pennsylvania team found participants who met the lower blood pressure target also had fewer signs of damage (cerebral white matter lesions) in brain scans. These lesions tend to accrue as we age and have been associated with a range of problems from balance to dementia. The findings were released last week at the annual Alzheimer’s Association International Conference in Chicago. The trials, dubbed the Systolic Blood Pressure Intervention Trial (SPRINT), were funded by the NIH, National Heart, Lung and Blood Institute, the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Neurological Disorders and Stroke.

Largest Trial of Prostate Cancer in African Americans
Researchers have begun recruiting thousands of patients for what organizers are calling the largest-ever study of aggressive prostate cancer in African-American men.The $26.5 million Research on Prostate Cancer in Men of African Ancestry (RESPOND) hopes to enroll10,000 participants and isolate environmental and genetic factors that seem to make black men especially prone to the cancer’s most aggressive forms. African-American men have a nearly 15 percent chance of developing prostate cancer (compared to about 10 percent for white men). Their risk of dying from the disease is about 4 percent (nearly twice the 2 percent for white men). RESPOND is led by researchers from the University of Southern California, University of California, San Francisco; Johns Hopkins (Baltimore), and the Dana Farber Cancer Institute in Boston. Funding comes from the National Cancer Institute, the National Institute on Minority Health and Health Disparities, the NIH and the Prostate Cancer Foundation.

Megabuck Autism Trials Set
A new international consortium has raised a record $132 million to research and treat autism. The Autism Innovative Medicine Studies (AIMS)-2-Trials brings together autistic people and their families, academic institutions, charities and drug companies to study autism (including possible links to heightened risk of other health problems like anxiety, depression and epilepsy) and develop new therapies. AMS-2 Trials will create the first European clinical trials network for autism — and pave the way for international government, industry and charity partnerships to quickly determine if drugs are effective. All autistic people are different. So the consortium is taking a precision medicine approach designed to tailor therapies to individual needs. AIMS-2-Trials has several financial backers, including the Innovative Medicines Initiative, Autism Speaks, Autistica and the Simons Foundation in New York. The Centers for Disease Control and Prevention earlier this year estimated that one in 59 children in the U.S. have autism, a 15 percent jump since 2016.

Drugs Targeting Parkinson’s May Help the Heart, Too
A drug being tested to treat Parkinson’s may also help heart failure, researchers have found. The drug, called ITI-214, is a phosphodiesterase type I inhibitor (a class of drugs that includes Viagra). During trials, it improved dogs’ and rabbits’ heart rate without lowering their systolic blood pressure, researchers reported in the July 20 edition of the journal Circulation. Heart failure affects about 5.7 million people in the U.S. It’s a condition in which the heart, a muscle, doesn’t do its job of pumping blood properly, depriving the body of oxygen and nutrients it needs. ITI-214 appears to suppress release of the enzyme PDE1, which can interfere with the heart’s ability to repair itself, according to researchers at Johns Hopkins and Duke University, who plan a clinical trial to test its effect in heart failure patients.

NIH Funds Clinical Trials in “Real-World” Settings
The National Institutes of Health has awarded more than $4 million for five clinical trials in “real world” settings. The funding was set aside to help researchers design clinical trials in places like emergency rooms and local clinics. If successful, the NIH says it would provide $31 million over the next five years for such studies.

New grant recipients include:

  • New York University for a trial on palliative care for senior patients in ERs;
  • Yale University to develop and test electronic health records systems to help ER doctors treat patients addicted to opioids;
  • University of Washington for a trial on a program to help children and teens deal with drug abuse and mental health problems;
  • University of Colorado, Denver to see if automated text messages or chat bots can help heart patients better adhere to medicine schedules; and,
  • Boston’s Dana Farber Cancer Institute for trials on a comprehensive advanced-care planning program for seniors with advanced cancer.

The NIH’s Health Care Systems Research Collaborator already supports nine trials being carried out in HMOs and other venues. The hope is that ERs, local clinics and the like can provide wide-scale research opportunities at lower cost.

Nonprofit Launches Clinical Trial Data-Sharing Platform
A nonprofit group has launched a data-sharing platform that organizers hope will allow researchers to find, manage, analyze and share data from clinical trials. Vivli’s data-sharing platform already includes information from some 2,500 studies submitted by 15 different organizations. It offers data on more than 1.3 million patients in 98 countries. The platform charges researchers $2,000 to share a single dataset. The Vivli platform is a Microsoft app. Organizers say the project evolved from work at the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University.

Researchers Halt Viagra Trials in Pregnant Women
Dutch researchers have pulled the plug on a trial testing whether sildenafil can help prevent low birth weight after at least 11 babies of participants died shortly after birth.Nearly 100 women had been given sildenafil (best known under its brand name, Viagra) while pregnant. Researchers had hoped to demonstrate the drug could dilate blood vessels in women with intrauterine growth restriction — a disorder in which a mother’s placenta restricts blood and nutrient flow to the fetus. The trial began in 2015 and was scheduled to run through 2020, according to published reports. Researchers had hoped to recruit 350 women through the trial. Some 183 women had already enrolled, with at least 93 taking Viagra and the rest on a placebo.

Personalized Immunotherapy Cancer Trials in the Works
Bristol-Myers Squibb and Gritstone Oncology are teaming up to conduct clinical trials on Gritstone’s GRANITE-001 personalized neoantigen immunotherapy treatment. Researchers plan to test the effect of a drug combination, including GRANITE -001 and Bristol-Myers’ Opdivo (a programmed death-1 immune checkpoint inhibitor), on patients with advanced solid malignant tumors. Some patients will also be injected with Yervoy, an immunotherapy. The companies hope to open a two-part, Phase I, dose escalation trial before the end of this year. GRANITE-001 is designed to help a patient’s T-cells attack mutation-derived, tumor-specific neoantigens.

EMA Adopts Revised Crohn’s, Colitis Drug Guidelines
The European Medicine Agency (EMA) has released new guidelines on developing treatments for Crohn’s disease and ulcerative colitis set to take effect Jan. 1. The drug recommendations for the two inflammatory diseases provide updated advice on considerations for non-generic treatments, including primary and secondary endpoints. The primary endpoint for studies of luminal Crohn’s disease (CD), which causes inflammatory changes in the lumen or tube of the intestine, and ulcerative colitis should be the co-primary evaluation of endoscopic and symptomatic remission, the agency says. The guidelines discourage using the Crohn’s Disease Activity Index (CDAI) to assess efficacy because of questions about its reliability and validity. Instead, symptoms and inflammation should be evaluated independently as co-primary endpoints. Sponsors should provide a direct comparison with a generally accepted standard first-line treatment when supporting a first-line indication for treating active CD, the guidance recommends. A placebo is an acceptable comparator for a second-line indication following failure or intolerance to primary therapy. But an active control may also be required, depending on the target population. The EMA’s Committee for Medicinal Products for Human Use adopted the two guidelines on June 28 and the agency officially posted them on its website on July 23. Read the revised Crohn’s disease guidance here: Read the revised ulcerative colitis guidance here:

WCG Acquires KMR Group, MCC
WCG, the leading provider of solutions to measurably improve clinical research quality and efficiency, has acquired KMR Group and Metrics Champion Consortium (MCC), global experts in clinical research benchmarking, metrics, analytics and performance management. “We are delighted to welcome the teams from KMR Group and MCC to WCG and excited to further solidify our role as the industry’s most powerful and reliable source for industry benchmarking,” says Donald A. Deieso, Ph.D, chairman and CEO of WCG. They join clinical trial market research leaders CenterWatch and FDANews to further boost WCG’s Market Insights and Intelligence Division, which provides a suite of trusted benchmarking, databases, market intelligence, reports, newsletters, books, conferences and webinars to guide industry decision makers.