From the Director - Update on Clinical Trials:
Dear Parents and Friends,
On June 28, 2016 Hoffman-La-Roche Ltd announced that it had suspended its ongoing clinical trial of Basmisanil (RG1662) in children with Down syndrome ages 6-11 years old.
According to their statement, “This phase II study did not meet its primary and secondary endpoints on improvement in cognition and function. There was no difference observed between adults (18-30 years old) and adolescent (12-17 years old) in the study. In addition, there was no significant difference between those who took the drug and those that took the placebo…. This pediatric study is not being discontinued for safety reasons as Basmisanil was well tolerated and no relevant safety signals were observed with Basmisanil when compared to placebo and previous trials.”
In my experience this was the best organized and most rigorously conducted clinical trial to date for persons with Down syndrome. The company expressed its disappointment by the lack of efficacy seen in the trial, as well as their gratitude to the families and researchers participating in this large multicenter study. Two equally ambitious, multicenter trials conducted by Pfizer/Eisai (2009-2010) using the compound Donepezil also demonstrated no benefit in adolescents and young adults.
So what are we to make of such developments? Clearly, it demonstrates that large scale clinical trials can be conducted in our community, and that recruitment of a large number of participants, while challenging, is very feasible. This is critically important because the biomedical research community and big pharma continue to focus on the development of novel pharmacologic treatments to improve language, cognition and adaptive function in persons with Intellectual disability. As an example of science in the public interest, our families, medical practitioners, and the Down syndrome community have been exceptionally well served by this important study.
While the findings are disappointing, it’s important to remember that we are at the earliest stages of the endeavor to discover the neurobiological underpinnings of cognitive and language dysfunction in people with Down syndrome. Leveraging these insights toward the development of effective treatments will require continued support and advocacy from within our community. Clinical trials, and related person-centered research, are well poised and ready for prime-time.>
George T. Capone, MD
Benefits of a Sleep Study:
The benefit of the interdisciplinary approach at the Kennedy Krieger Institute is that we are often able to meet your child’s needs that are beyond the scope of our clinic by referring to other departments within the Institute. The DSCRC works closely with the Kennedy Krieger Sleep Disorders Clinic and Lab to ensure that our patients who have sleeping difficulties are able to get a comprehensive evaluation and treatment plan. The new co-directors of the Sleep Disorders Clinic are Janet Lam, M.D., medical director and Valerie Paasch, Ph.D, behavioral psychology director.
The clinic recently created a social story picture narrative for childrenbecause they recognized that most parents are not familiar with all of the components of a comprehensive sleep study. “We want to inform families about what is involved in an overnight sleep study and let kids see (in a child-friendly way) what they will experience during the procedure. Additionally, we recognize that a sleep study is difficult for many children to complete and wanted to provide easy access to professional support from our Behavioral Pediatric Psychology Program (on second page of story) if parents feel their child would benefit from additional preparation before participating in a sleep study.” – Valerie Paasch, PhD
If your child is scheduled to have a sleep study, the child-friendly presentation mayhelp your child understand the details of the process and ease some anxiety about the overnight stay. Click here to read or download a copy of the sleep study story. It may be the first step to your child having a good night’s sleep!
Improving healthcare and research opportunities for people with Down syndrome is a consuming task. Dr. Capone frequently speaks to parents, health professionals, educators, therapists, and patrons about the clinic, its research projects, and the latest findings from the DSCRC. Dr. Capone presented at the following events:
The IV Iberoamerican Congress, sponsored by the Federacion Iberoamerican de Sindrome de Down in Salamanca, Spain in March, 2016. Dr. Capone was the keynote speaker on “Healthcare for Adults with Down Syndrome” and served on a panel discussion on “Developmental, behavioral phenotypes and maladaptive behavior in children with Down syndrome.”
Dr. Capone also attended the Down Syndrome Medical Interest Group (DSMIG) Annual Symposium in Orlando, Florida in July, 2016. DSMIG-USA is an organization for professionals who work in the field of Down syndrome. The conference serves an in interdisciplinary forum for sharing knowledge and experiences related to the clinical care of children and adults with Down syndrome. It is held each year in conjunction with the National Down Syndrome Congress (NDSC). This year, Dr. Capone received a surprise award voted on by his professional peers in the Down syndrome community. Along with Kim McConnell, M.D. from Gillette Children’s Hospital, he was honored as co-recipient of the “William I Cohen, M.D. Distinguished Service Award”
Dr. Capone also presented “Common Behavioral Issues in Children with DS+ASD” for parents and therapists who serve children with this dual-diagnosis. Reflecting on his over 20 years attending the NDSC conference, he stated, “It’s always fun to see so many familiar faces from the community who attend the NDSC conference on a regular basis. They are the glue that keeps us connected”
A Family's Story - Congratulations:
By Debra Grimm
Twenty-one years ago, my twin daughters, Cheyenne and Dakota, were born premature. A team of doctors in their white lab coats lined up at the bottom of my bed and told me, “I‘m sorry, but your daughters have Down syndrome.” Instead of congratulating me on the birth of my beautiful babies, doctors told me that, since I was a single parent, the twins would be a burden to me and I should give them up for adoption. They assumed I would not be able to provide the care my daughters needed. I was also told my daughters would never be able to walk or talk. I knew better, and told them, “My girls are going home with me.”
When I brought Dakota and Cheyenne to Kennedy Krieger, I experienced a completely different mindset. At my first visit with Dr. Capone at the Down Syndrome Clinic and Research Center, he made it a point to congratulate me, which was very heartwarming and much-needed. That was the first time I had heard that, and the girls were 6 months old. Dr. Capone was the complete opposite of the doctors I had met before. He said my girls would walk and talk and do everything that other children would, only at a much slower pace. Kennedy Krieger gave me hope—not that they were going to cure my children—but hope in what my children could do, that they had potential and expectations just like every child has.
The girls received occupational, physical, and speech-language therapy at Kennedy Krieger, and I worked with them every day. I remember the therapists asking if I was a therapist, because I was already using some of the therapy techniques instinctively. For example, as an infant, Cheyenne would turn her head only to the right, so I talked to her from her left side so she would turn. Children with Down syndrome have a tendency for their mouths to hang open, so I would touch my girls’ chins so they would close their mouths.
I also started teaching the girls sign language. At daycare, the teachers were surprised to see Dakota and Cheyenne sign ‘Mom’ when they heard my voice. They were learning more each day, and by age 4, the girls were talking and walking. Soon they began school, where they continued to thrive.
Today, my girls attend Baltimore County Public Schools, and are involved in Special Olympics, cheerleading, bowling, and soccer. Cheyenne is the class clown—she loves to make her teachers and classmates laugh. She hopes to find a job working with animals. Dakota is artistic, and wants to be a chef. They are realizing the potential that I knew they had.
Safety and efficacy of rivastigmine in children with Down syndrome: A double blind placebo controlled trial.
Individuals with Down syndrome (DS) have an uneven profile of cognitive abilities, with more pronounced deficits in learning, memory, and expressive language. Studies of cholinesterase inhibitors in children with DS have been limited. This study aimed to: (i) investigate the safety and efficacy of rivastigmine treatment; (ii) build upon our previous open-label studies in children with DS; and (iii) investigate specific cognitive domains that may respond to rivastigmine treatment. The results did not demonstrate evidence for significant improvement in cognition, language, or overall function in the children receiving rivastigmine. Our results suggest that rivastigmine is safe and well-tolerated for children and adolescents with DS, but may not be effective for improving performance on the selected measures in this study.
Gail A. Spiridigliozzi, Sarah J. Hart, James H. Heller, Heather E. Schneider, Jane Ann Baker, Cathleen Weadon, George T. Capone, Priya S. Kishnani (2016) Safety and Efficacy of Rivastigmine in Children with Down Syndrome: A Double Blind Placebo Controlled Trial, American Journal of Medical Genetics. AJMG doi:10.1002/ajmg.a.37650
Signs of aspiration in adults with Down syndrome
Pneumonia and aspiration pneumonia are major causes of mortality in adults with Down syndrome (DS). However, dysphagia and swallowing safety have not been well studied in this population. Our aim was to examine the prevalence of aspiration signs in adults with DS using caregiver reports of swallowing-related concerns and a water-swallowing screen. Only 4 of the 26 participants (15.4%) had no signs of increased aspiration risk during testing. Eighteen participants (69.2%) screened positive during trial 1. Caregivers reported a comparable prevalence, providing converging evidence of high aspiration risk. The prevalence of aspiration signs within this cohort of young, otherwise healthy adults with DS was comparable to that of high-risk patients reported elsewhere. Therefore, results support the hypothesis that swallowing dysfunction and aspiration may contribute to a risk for pneumonia in this population.
Jasien, JM, Capone, G, Silverman, W., Shapiro, B, K, Weadon, C., Rivera, T. and Gonzalez-Fernandez, M. (2016) Signs of aspiration in adults with Down syndrome. J NeurolNeurobiol 2(2): doi.org/10.16966/2379-7150.120
Outcome Measures for Clinical Trials in Down Syndrome
Increasingly, individuals with intellectual and developmental disabilities, including Down syndrome, are being targeted for clinical trials. However, a challenge exists in effectively evaluating the outcomes of these new pharmacological interventions. Few empirically evaluated, psychometrically sound outcome measures appropriate for use in clinical trials with individuals with Down syndrome have been identified. To address this challenge, the NIH assembled leading clinicians and scientists to review existing measures and identify those that are appropriate for trials, and areas where new measures need to be developed. This paper focuses on measures in the areas of cognition and behavior.
Anna J. Esbensen, Stephen R. Hooper, Deborah Fidler, Sigan Hartley, Jamie Edgin, Xavier Liogier d’Ardhuy, George Capone, Frances Conners, Carolyn B. Mervis, Leonard Abbeduto, Michael Rafii, Sharon J. Krinsky-McHale, Tiina Urv, and Outcome Measures Working Group (2016) Outcome Measures for Clinical Trials in Down Syndrome, American Journal of Intellectual and Developmental Disability (AJIDD in press)
"Relaxation at the Vine" Fundraiser Update:
Thanks so much to everyone who sponsored, volunteered for, and attended the second annual Relaxation at the Vine event this past spring. We enjoyed the unique selection of Boordy Vineyards wines and were surrounded by a beautiful landscape, all while supporting a great cause. There were exciting raffle prizes and auction items, delicious catered food, music, and a photo booth. It was a fun and memorable occasion. Through your generosity, more than $6,000 was raised to benefit the research efforts of the Down Syndrome Clinic and Research Center (DSCRC).
Please stay tuned for information on future events.
Please Participate in Our Survey:
The DSCRC helps all patients reach their full potential and function as independently as possible in family, school, and community life. We would like to continue to serve our families in the community through social events to bring families together. To that end, we have put together a survey about what events and social activities would be of interest to you. Your feedback about how the DSCRC can best serve your needs, and better serve families with a loved one who has Down syndrome, is appreciated.
Support the Down Syndrome Clinic and Research Center:
Your financial gift ensures that children, adolescents, and adults with Down syndrome are able to participate in studies designed to advance treatment now and in the future.
Adults with Down Syndrome Needed for Study on Depression and Sleep Disorders:
Kennedy Krieger is recruiting individuals with Down syndrome ages 18-30 years with mental health concerns, such as loss of functional skills, low motivation, depressed mood, social withdrawal, and motor slowing. We are also recruiting individuals with Down syndrome without mental health concerns or functional decline.
We cannot accept individuals with aggressive, disruptive, or non-compliant behaviors. All subjects will receive a comprehensive evaluation assessing general level of function, behavior and mental health, and sleep quality, as well as body shape/proportion and dietary/nutritional status. The study will include a sleep study and collection of urine, saliva, and a morning blood sample for biochemical testing.
The goal of the study is to improve our understanding of the relationship between sleep, stress, metabolism, and mental health in persons with Down syndrome. The study requires one extended visit over a two- to three-day period, including one overnight visit at the Johns Hopkins Clinical Research Center. There are minimal risks and no direct medical benefits for participating. You will receive medical test results that may be of interest to you or your physician. A cash incentive is offered for your participation.
We will try our best to accommodate your schedule.
Study sponsor: The Johns Hopkins Institute for Clinical & Translational Research
PI: Dr. George Capone
Protocol Number: NA_00018279
Baltimore Buddy Walk:
The DSCRC is honored to be invited to participate in the 2016 Baltimore Buddy Walk on Saturday October 22, 2016 from 8am-noon. Thank you to the Chesapeake Down Syndrome Parent Group for your invitation to help sponsor and attend this event. Please visit the DSCRC’s table to learn more about the clinic and to participate in a fun activity! There will be fun for the whole family at the walk, including music by Milkshake, food, games, moon bounce, face painting, characters, entertainment, and advocacy and resource information. You do not want to miss this. Please visit www.baltimorebuddywalk.org to sign up.