By Michelle A. Cissell, Ph.D.
Women know the importance of taking extra care of themselves before and during pregnancy—for the optimal health of their babies, as well as for their own well-being. For women with type 1 diabetes (T1D), diligent self-management both before and during pregnancy is especially crucial, as high blood glucose levels increase the risks to both mother and baby. In keeping with its commitment to helping people with T1D at all ages and all stages of the disease, JDRF is launching the CONCEPTT clinical trial in partnership with JDRF Canadian Clinical Trial Network (JDRF CCTN). CONCEPTT aims to determine whether the use of real-time continuous glucose monitoring (CGM) will facilitate improved glucose control in women with T1D who are pregnant or planning to become pregnant—a finding that would have wide-ranging benefits for mothers with T1D and their babies.
Type 1 diabetes and pregnancy
Poorly controlled T1D during pregnancy carries extra risks that can affect both mother and baby. Women with diabetes—either T1D, type 2 diabetes (T2D), or gestational diabetes—are more likely than women without diabetes to develop preeclampsia, a condition characterized by dangerously high blood pressure, and to experience labor and delivery complications. Babies of women with diabetes are at greater risk for complications such as macrosomia (excessively high birth weight), premature birth, and shoulder dystocia—a birth complication that can result in permanent nerve damage and other issues. These babies may also be at greater risk of developing T2D later in life.
Fortunately, research has shown that good blood-glucose control during pregnancy can reduce the excess risks caused by diabetes and promote healthy outcomes for mother and child. But tight control is not always easy to achieve during pregnancy, even for women who test their blood glucose numerous times throughout the day. Researchers now face the challenge of closing the gap between the clinical ideal of near-normal glucose control and the levels of control that pregnant woman are actually able to achieve in real life.
The promise of continuous glucose monitoring (CGM) in diabetes and pregnancy
Helen Murphy, M.D., a clinician-scientist at the University of Cambridge, in the United Kingdom, and her colleagues showed that using CGM as an educational tool during pregnancy helped women with T1D and T2D to achieve better glucose control and also reduced the risk of macrosomia in their babies. In that study, the CGM data were blinded, meaning that the women in the study could not see their blood-glucose levels as they were being measured by the device. Instead, the CGM devices were returned to study investigators, who downloaded a week’s worth of blood-glucose measurements and used that information to counsel the women on how to adjust their diabetes management practices. “We could show that with access to CGM, which was only once per trimester, we were able to help the women improve their blood sugars and that improvement was sufficient to impact on pregnancy outcomes,” explains Dr. Murphy. “However, it [also] told us that it wasn’t enough to get pregnancy outcomes back to what we’d ideally like them to be.”
While Dr. Murphy’s study was under way using blinded CGM, a team of JDRF-supported researchers showed in a landmark trial that continuous access to blood-glucose levels in real time significantly improved blood-glucose control in adults with T1D, including non-pregnant women. Real-time CGM devices feature technology that displays a person’s blood-glucose levels when a measurement is taken every few minutes. Could real-time CGM devices be the key to closing the gap between ideal and actual blood-glucose control during pregnancy? And could the use of these devices increase healthy outcomes in pregnant women with T1D?
To answer those questions, JDRF leveraged its unique position as the global leader in T1D research and advocacy to convene a workshop of scientific experts in the field of T1D and pregnancy. The researchers were asked to design a clinical trial testing the use of real-time CGM before and during pregnancy in women with T1D. CONCEPTT, the trial that emerged from that workshop and subsequent discussions, is an international, multicenter clinical trial that seeks to establish the benefits of real-time CGM in T1D and pregnancy. Denice Feig, M.D., head of the Diabetes and Endocrinology in Pregnancy Program at Mount Sinai Hospital in Toronto, serves as the principal investigator for CONCEPTT. “Women with type 1 diabetes work very hard to have healthy pregnancies, but we still have a way to go to make these pregnancies as healthy and low-risk as possible,” states Dr. Feig. “We’re excited about this trial because we’re hoping that the continuous glucose monitors will help women achieve really excellent glycemic control without too many low blood sugars, which will help [improve] pregnancy outcomes.”
Active recruitment for CONCEPTT will begin later this year. CONCEPTT will enroll two groups of women in a randomized clinical trial. One group will include 110 women with T1D who are planning to become pregnant. This arm of the trial will provide a unique look at blood-glucose control in the weeks immediately before and after conception. A second group will include 214 women with T1D who are less than 14 weeks pregnant. Women in each group will be randomly assigned either to receive real-time CGM in addition to their standard intensive insulin regimen or to continue with their intensive regimen without CGM. According to Dr. Murphy, a co-principal investigator of the trial, “CONCEPTT will establish whether or not there is a benefit of real-time CGM in addition to very intensive blood-glucose testing, and whether that benefit is equal between women who plan their pregnancies and start the CGM before pregnancy, or [if] starting during pregnancy is just as effective.”
The CONCEPTT trial is a key part of JDRF’s research commitment to improve treatment for T1D for people at all ages and all stages of the disease. Marlon Pragnell, Ph.D., JDRF senior scientific program manager of glucose control therapies, notes that CONCEPTT represents an exciting use of CGM in an extremely motivated population. His expectations are high. “This study will also lead to a comprehensive understanding of blood-glucose control in pregnant women throughout pregnancy and, very importantly, inform future studies on closed-loop systems,” he says. “Moreover, the trial could support JDRF’s advocacy efforts related to CGM use in T1D.”
To date, the scientific evidence has not been strong enough for most governments or insurance carriers to endorse CGM as the medical standard of care in women with T1D during pregnancy. In the United States, CGM use may be covered by insurance, but medical guidelines recommend CGM as only a supplementary tool during pregnancy. In many European countries, there is no evidence of widespread CGM use or insurance coverage for CGM in T1D during pregnancy. CONCEPTT is an international trial that will be conducted in multiple centers with women of different cultures and ethnicities. Thus, CONCEPTT has been designed to provide the robust data needed to establish CGM as the uniform standard of care in T1D and pregnancy in many countries around the world. The impact of this international trial could be widespread. A successful outcome would support JDRF’s efforts to advocate government and healthcare insurance approval and reimbursement of CGM use in pregnancy. Equally important, positive results from the CONCEPTT trial could convince more healthcare providers to encourage CGM use and make it available to their patients with T1D who are pregnant or planning a pregnancy.
A true collaboration for healthy pregnancy
CONCEPTT is a truly collaborative effort on many levels. “The strength of the trial comes from the intellectual contributions of multiple partners working together to ensure the healthiest possible pregnancies for women with type 1 diabetes,” says Olivia Lou, Ph.D., JDRF scientific program manager of international partnerships and program officer for JDRF CCTN.
JDRF is funding the trial in partnership with JDRF CCTN, which itself is a partnership between JDRF Canada and the Canadian government. Established in 2009, JDRF CCTN is a groundbreaking effort to accelerate solutions for the management, care, and cure of T1D. Bringing together Canada’s top physicians, scientists, researchers, and innovators from leading hospitals, academic medical centers, and industry, JDRF CCTN (www.jdrf.ca/cctn) is currently developing several high-profile clinical trials, in association with leading diabetes researchers at partnering universities and medical centers in southern Ontario.
To complement the Canadian network, JDRF is supporting an international group of leading investigators in the United States, Europe, and Israel. An international group of more than 20 leading investigators is contributing to the rigorous design and implementation of the CONCEPTT trial.
The challenges of blood-glucose control that women with T1D face during pregnancy are not trivial. Anything that can be done to help pregnant women achieve near-normal control will have enduring benefits for both mother and child. JDRF, in partnership with JDRF CCTN and a community of dedicated researchers, is committed to evaluating the most state-of-the-art technologies for diabetes management in this special population. If successful, CONCEPTT has the potential to change pregnancy care in women with T1D almost immediately with technologies that are available now. All of the trial partners are hopeful that this trial can provide the evidence needed to validate real-time CGM as a critical tool for promoting healthy outcomes for all pregnant women with T1D and for their babies.