Coming Attractions: Top Endocrinology Clinical Trials at NIH

The National Institutes of Health funds billions of dollars in medical research each year and many of the studies will have profound effects on the practice of endocrinology. Here’s an overview of some of the leading endocrine-related studies currently taking place. 

Medical knowledge marches forward one study at a time. The National Institutes of Health (NIH) oversees perhaps the premier medical research program in the world, involving billions of dollars. NIH develops and tests many cutting-edge therapies, but also concentrates on plugging the gaps in knowledge that private entities will be unlikely to fund, such as new uses for generic drugs, the effectiveness of dietary supplements, and head-to-head comparisons of drugs made by different companies, says Judith Fradkin, MD, director of the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases.

Here is a very small sampling of the most intriguing and anticipated trials related to endocrinology, chosen in consultation with the Endocrine Society’s Research Affairs Core Committee and NIH staff .

Sex Hormone Treatment

Testosterone supplementation has been advertised so heavily that “low T” has become a catch phrase, without much hard data about its efficacy. The multicenter Testosterone Trial involves men 65 years and older who have low blood testosterone and at least one accompanying problem. Some 800 men were randomized to receive testosterone gel or placebo in six trials of the treatment’s effects on physical function, vitality, sexual function, cognitive function, anemia, and cardiovascular risk. Results will begin appearing later this summer, so physicians will have a better evidence base for responding to patients prompted to “ask your doctor.”
The clinicaltrails.gov identifier: NCT00799617

On the women’s side, Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH), is a network of researchers conducting randomized clinical trials to test a variety of approaches for treating menopausal symptoms like hot fl ashes, sleep disturbance, mood disorder, and sexual dysfunction. Most of the early findings have shown that many widely used over-the-counter treatments are ineffective — important findings because “these were things people were spending gazillions of dollars on,” according to Nanette Santoro, MD, E. Stuart Taylor Chair of Obstetrics and Gynecology at the University of Colorado School of Medicine in Aurora.
Various studies are continuing to enroll patients at five research centers around the country.

For information, visit http://msflash.org.

Vitamin D Trials

“The rate of prescriptions for vitamin D has gone up astronomically. It has become a very popular treatment without a lot of hard evidence, so clinical trials are important,” Fradkin says.

The VITamin D and OmegA-3 Trial (VITAL) is a randomized trial of almost 26,000 U.S. men over 50 and women over 55 investigating whether taking daily dietary supplements of 2000 IU of vitamin D3 or 1 gram of omega-3 fatty acids reduces the risk of developing cancer, heart disease, and stroke in people who do not have a history of these illnesses.

The study began enrolling subjects in 2010 and has filled its quota, with an expected completion date of October 2017.
The clinicaltrials.gov identifier: NCT01169259

Observational studies suggest that vitamin D may lower the risk of developing type 2 diabetes. The VITamin D and Type 2 Diabetes Trial is testing whether a vitamin D supplement can prevent or delay the onset of type 2 diabetes in adults 30 and older who have prediabetes. It should also improve understanding of how vitamin D affects glucose metabolism. Researchers at 20 sites around the country will randomize about 2,500 volunteers who have a BMI of 24 to 42 and other diabetes risk factors to receive either a once daily vitamin D3 soft gel or a placebo for three years. The daily dose of 4,000 IUs of vitamin D is much higher than the 600 to 800 IUs recommended by the Institute of Medicine. The study began enrolling subjects in late 2013, and enrollment will take about two years.
The clinicaltrials.gov identifier: NCT01942694

Comparing Diabetes Treatments

Metformin is the first choice among drugs for treating type 2 diabetes, but most patients will progress to needing another drug as well. There is a large variety of these drugs, but a dearth of information on which work the best with metformin. Glycemia Reduction Approaches in Diabetes: A Comparative Eff ectiveness Study (GRADE) is open to patients 30 years and older on metformin who developed type 2 diabetes within the past 10 years. Participants will be randomly assigned to one of four commonly used glucose-lowering drugs in addition to their metformin: glimepiride, sitagliptin, liraglutide, or basal insulin glargine. They will be followed for up to seven years to determine the best combination for glycemic control, side effects, and overall health. Forty-four clinical sites have enrolled almost 1,700 of a projected 5,000 participants.
The clinicaltrials.gov identifier: NCT01794143

Preventing Beta Cell Loss

The Restoring Insulin Secretion (RISE) study is a set of small trials testing methods to improve and preserve the production of insulin in people who have prediabetes or have been recently diagnosed with type 2 diabetes.

Two of the trials will examine whether these patients should be treated sequentially — adding drugs as needed — or whether more aggressive initial treatment could give the insulin-producing beta cells a chance to rest and restore function.

A trial for adults will compare a placebo to three drug regimens: metformin alone, metformin plus liraglutide, and glargine used for three months before switching to metformin.
The clinicaltrials.gov identifier: NCT01779362

A trial in youth aged 10 to 19 will compare metformin alone to a regimen of using glargine for three months before switching to metformin.
The clinicaltrials.gov identifier: NCT01779375

A Gout Drug for Kidney Disease?

Preventing Early Renal Loss (PERL) in type 1 diabetes is the kind of study that no pharmaceutical company could profit from: a new use for a cheap drug used to treat gout for 30 years. Diabetic kidney disease is a huge problem, and studies indicate that moderately elevated serum uric acid may play a pathogenic role. Allopurinol has been used for many years to decrease high blood uric acid, so this trial will test its efficacy in maintaining kidney function in people with type 1 diabetes early in the course of kidney disease. The international trial began enrolling patients in early 2014, aiming for 480 patients at 13 diabetes centers. Patients are randomly assigned to take allopurinol or placebo for three years to see whether the drug slows the loss of kidney function.
The clinicaltrials.gov identifier: NCT02017171

Special Funding for Type 1 Diabetes

NIH has a special annual $150 million appropriation recently extended through 2017 — advocated for by the Endocrine Society — for research into type 1 diabetes that is allowing it to undertake “big bold things that we would not otherwise be able to do,” NIH’s Fradkin says.

In one initiative, researchers screened almost half a million newborns to find people with the high risk HLA genotype, which led to the enrollment of 8,000 children to monitor and analyze environmental factors that might contribute to the development of type 1 diabetes.

Another study has screened some 1.5 million family members of people with type 1 diabetes to enroll people in several ongoing trials of strategies to prevent the progression from autoimmunity to type 1 diabetes. The studies are run under the auspices of an international network of researchers known as TrialNet, which includes 18 centers running clinical trials and more than 150 participating medical centers and physicians’ offices.
For information, visit www.diabetestrialnet.org/studies/

NIH is also investing millions in trials testing the development of several “artificial pancreas” models, but space considerations dictate that these important trials will be covered in a future issue of Endocrine News.

— Seaborg is a freelance writer based in Charlottesville,
Va. He wrote about the microbiome in the May issue.

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