The Trial to Reduce IDDM in Genetically at Risk · Trial to Reduce IDDM in the Genetically at Risk TRIGR Family News Autumn 2007 Trial to Reduce IDDM in the Genetically at Risk Aims

Trial to Reduce IDDM in the Genetically at Risk

TRIGR Family NewsAutumn 2007www.trigr.org

Trial to Reduce IDDM in the Genetically at Risk

AimsThe overall objective of the TRIGR study is to determinewhether weaning to a highly hydrolyzed formula in in-fancy reduces the risk of Type 1 diabetes in childrenwith increased genetic risk of developing the diseaseduring the first 10 years of life.

We have recently reached a very important milestone,thanks to all study families. Altogether 2161 families arein the study and that will be enough to give us the an-swers we are looking for.

Country Families within the Study

Australia 101

Canada 529

Czech Republic 164

Estonia 34

Finland 424

Germany 112

Hungary 23

Italy 54

Luxembourg 7

Netherlands 53

Poland 95

Spain 60

Sweden 97

Switzerland 13

United States 395

Total 2161

The most important issue for the study is now in yourhands. Please make your study follow-up visits asplanned, and be active at your visits. Our study centersare very willing to give you all the support and to answerall questions related to the study.

Matti KoskiChief EditorTRIGR International Coordinating Center

Everyday, medical researchers and families like yours,work together to collect key clinical data for significantinvestigations to advance type 1 diabetes research.This vital collection of data in studies such as oursbroadens the resources available to researchers whoare working constantly to uncover the mysteries of thisdisease.

There are three primary groups that comprise the datacollection team of our international TRIGR Study. Thetwo most noticeable are the participants and their fami-lies (you) who volunteer their time and efforts to takepart in the study, and the physician-investigators andstaff – the nurses, dieticians and support staff – inTRIGR’s clinical study centers.

David Cuthbertson, biostatistician; Jeffrey Krischer, P.I.; LindaShanker, project coordinator; Bruce Gainer, computer applica-

tions developer; Rob Gowing, systems administrator

The team is not complete, however, without a third es-sential component: the TRIGR Data Management Unit,or DMU. TRIGR’s DMU is located at the Pediatrics Epi-demiology Center (PEC) of the University of South Flor-ida in Tampa, Florida, USA. It is headed by JeffreyKrischer, Ph.D., who is the director of the PEC as wellas professor and chief of the Division of Bioinformaticsand Biostatistics in the university’s medical school. Dr.Krischer and his PEC team have significant experienceproviding data management, statistical analysis andother coordinating and supporting services to numerousmulti-site and international clinical studies, such as DPT-1 (Diabetes Prevention Trial of Type 1 Diabetes) andTEDDY (The Environmental Determinants of Diabetes inthe Young Study), among others.

Put simply, the DMU stores and safeguards TRIGR’s

Editor’s Corner Behind the Scenes with TRIGR’sData Management Unit

centralized bank of the dietary, physical (height, weight,etc.), blood draw data and other study information fromor about your child and the other children participating inTRIGR. DMU also furnishes tools to our TRIGR re-searchers to make it easy for them to input and reviewvital study information. Besides maintaining on-lineforms that facilitate data-entry efficiency while reducingrisk of errors, the DMU provides compliance and statisti-cal reports and other support to the study – and gener-ally helps TRIGR to be as effective as possible.

Yesterday vs. Today

Prior to TRIGR, data collected by researchers in multi-site clinical trials typically were recorded by hand, thenfaxed or mailed to a data managing group, where thedata would be entered into a database. Accessing par-ticipant data often meant manually preparing, printingand mailing reports to researchers for review. In suchan environment, especially with sites at great distances,working with clinical data was frequently tedious, ineffi-cient and expensive.

Since our start in May 2002, TRIGR has led the waywith easier and more efficient data storage, access andreporting through use of innovative, customized com-puter programs and centralized data management –including the maintenance of a secure and confidentialstudy-wide database and a private internal website foruse solely by authorized TRIGR researchers.

Maintaining a Secure and Confidential Website forData Entry

By its nature, the Internet provides flexibility for peopleto communicate quickly, regardless of location, be itcountry, continent or time zone. TRIGR takes advantageof this flexible medium by having an encrypted, pass-word-protected website through which our clinical re-searchers around the world enter and retrieve partici-pant data and general study information at their conven-ience, wherever they are. This saves our researcherssubstantial time, while protecting our participants’ pri-vacy. It also reduces excessive use of paper and otherexpenses.

Assuring Data Integrity

For TRIGR ultimately to reach reliable conclusions, it iscrucial that our researchers collect accurate and com-plete information from and about our TRIGR childrenand their families – and then record the data accuratelyand completely. You and your TRIGR child help by hav-ing timely follow-up visits, allowing periodic blood draws,

and giving honest responses to your local study center’sinquiries. Without your cooperation, we will not havesufficient and reliable data to analyze. But with yourinvolvement, the study can be a success.

Similarly, the study centers and laboratories must recorddata correctly and promptly. In this regard, the DMU,working closely with local sites, study laboratories, re-gional monitors and oversight committees, produces avariety of monitoring reports and reminders on an ongo-ing basis. To ensure data quality and integrity, the DMUalerts the monitors, sites, laboratories and committeesabout such matters as missing or incomplete data, pos-sible data-entry discrepancies, or similar complianceitems to be verified or corrected.

The DMU is committed to ensuring the confidentiality ofthe data submitted to the study database. Participantsare identified in the study database by special codes --not by name, address or other direct identifiers. More-over, access to particular participant data is restricted toTRIGR researchers who have been specifically author-ized.

Providing Study Tools and Resources

In addition to creating the on-line data-entry forms, theDMU disseminates internal policies, news and studymaterials to help TRIGR researchers be aware of studyrequirements and procedures. Analysis of clinical datais a vital aspect of any study, and the DMU also pro-vides statistical support to the study. Among otherthings, compliance and similar reports are provided tostudy centers, oversight committees and monitors. Inaddition, the DMU may provide certain generalized, pre-liminary information, such as growth or dietary summa-ries, vaccination information, or health events, to appro-priate TRIGR researchers, study monitors, and over-sight committees for review. Over time, as the studyprogresses toward completion, the DMU will perform in-depth data analyses.

Tomorrow and the Years Ahead

The TRIGR Study expects to continue collecting datainto the year 2017, when our youngest participantsreach 10 years of age. Throughout this time, the DMUwill continue to support our important clinical trial byproviding TRIGR researchers with useful study formsand tools, safeguarding participant information, monitor-ing the recording and accuracy of the data, and produc-ing significant reports and analyses.

Although the DMU works “behind the scenes”, it is anessential part of the international TRIGR team. We areproud of the vital service that the DMU performs in ourefforts to answer the significant TRIGR questions and toadvance research in the fight against diabetes.

Linda Shanker, Project Coordinator, DMU and Jennifer Lloyd,Information & Publication Services Coordinator, PediatricsEpidemiology Center

The transition from breastfeeding to family foods typi-cally covers the period from 4 to 18-24 months of age.The eating patterns in early childhood are influenced byparental eating habits. Healthy eating patterns shouldstart in infancy. Choosing healthy foods for your child,including nutritious snacks and meals, avoiding sugarand soft drinks, and maintaining a consistent feedingpattern helps to create healthy eating habits. Offering awide variety of healthy foods and motivating your childto taste them teaches the child to get used to differenttastes and new foods. Add variation of foods step bystep in order to get your child used to different tastes.

Three major meals (breakfast, lunch and dinner) andtwo-three snacks between the meals are recommended.Children cannot eat big portions and therefore small butfrequent meals are adequate to avoid tiredness betweenthe meals. How-ever, eating con-stantly during theday is not recom-mended. When of-fering the meal, tryto set the tablenicely and try tocreate a positiveand peaceful mo-ment for eating. It isgood to rememberthat the parents de-cide the food to betaken and the childdecides the amount of food to be taken. Children have agood regulatory system for food intake and they haveability to express their satiety. If a child does not eat wellat lunch, perhaps she/he eats better at dinner, or on thefollowing day. A healthy child does not suffer if she/hesometimes eats less.

When your child gets older, she/he will have her/hisfriends’ birthday parties or other parties to join. Andmost probably you also have to arrange some parties foryour child. We have collected for you some easy andhealthy foods that can be served at children’s parties.

Roasted pumpkin seedsRoast the pumpkin seeds in a dry frying pan or in theoven until they are golden brown.Sprinkle with your choice of seasonings, for examplegarlic powder or cinnamon.

Mini PizzasSlices of bread or bagelsTomato sauceMozzarella cheeseVegetables (broccoli, zucchini, onions, etc.)Preheat the oven 200 °C/350 FSpread tomato sauce on each bread/bagel half, top withcheese and vegetablesPlace on baking sheet.Bake for about 10 minutes or until the cheese hasmelted.

Vegetable skewersCherry tomatoes, pineapplebites, sweet pepper, zucchini,broccoli

Serve with light dip sauce(natural yoghurt mixed withspices and herbs)

Fruit skewersStrawberries, watermelon,bananas, kiwi, apple, cherries(remove the stone), plums,pears

Serve with ice cream or with vanilla custard.

Katriina Koski, European Study Monitor; Eeva Pajakkala, Eu-ropean Study Monitor; Susa Sorkio, Research Fellow

Helping Young Children Cope with the Blood DrawBlues

Distraction Techniques for Young ChildrenBreinne Regan, MS, CCLS

It is very common for young children to have a fear ofneedles. For some children, even the thought of havinga “poke” upsets them. Many children may experienceanxiety during blood draws which can cause them tokick, scream and sometimes bite. When children areupset, it can make the blood draw difficult for the healthcare professional, the parents and the child. A difficultblood draw can produce negative memories for thechild, and these memories can remain with the child formany years. Blood draws can be an unpleasant experi-ence for children, their parents and health care profes-sionals.

Although blood draws can be difficult for children, thereare various ways to help them cope with the experience.Here are some tips that may help when a child is havinghis or her blood drawn.

Nutrition Corner

TRIGR in the United States

• Bring familiar objects from home such as ablanket or favorite toy. These items help providea sense of comfort and security for the child.

• Ask the child if he or she wants to watch. Somechildren want to watch; others would rather lookaway. If the child does not want to watch, havean alternate focus in mind, such as looking at aninteresting book or pictures on the wall.

• Let the child know what is going to happen. Letthe child know who may be in the room, what heor she may see, hear, smell and feel. Preparingthe child for the experience can decrease anxi-ety.

• Parents are strongly encouraged to stay andhelp their child during a blood draw. Parents canhelp provide physical comfort, distraction, andassistance.

• Provide positive reinforcement and praise duringand after the blood draw. Using phrases like“you’re holding so still, what a great helper youare” or “Great job, I’m so proud of you!” canprove to be quite helpful.

• Use distraction. Distraction can be anythingfrom talking with the child to blowing bubblesand singing songs. Distraction techniques varybased on the child’s age as well as interests.When distracting a child be sure to remain at hisor her eye level and to talk in a calm and sooth-ing voice. Here are some distraction sugges-tions for the various age groups.

o Infant: bubbles, mirrors, musical andchime toys, rattles, squeak toys, stack-ing toys, pop up toys, tub toys and pic-ture books.

o Toddler: bubbles, blocks, music, pin-wheels, puppets, pop up books, soundtoys, paper party blowers and magicwands.

o Preschooler: bubbles, puppets, pop upbooks, music, magic wands, wheeledtoys, play dough, pinwheels, storybooks and stickers.

There are many ways to distract a child. If you do nothave any toys with you, be creative. A couple of cottonballs can easily become snowballs, or a tourniquet canbecome a snake. Use your imagination and the possi-bilities are endless.

These techniques prove to be quite helpful in reducinganxiety and fear in children who are having their blooddrawn. Just remember to remain calm, talk in a quiet,soothing voice and use various distraction techniques.

Breinne Regan is a Certified Child Life Specialist. For moreinformation on coping and distraction or the Child Life profes-sion, visit the Child Life Council athttp://www.childlife.org

The Williams family

Our family lives in the Illawarra area on the South Coastof New South Wales. It is a beautiful part of Australiawith plenty of things to do. We are only a short driveaway from the ocean and an even shorter walk to LakeIllawarra.

When I was told about TRIGR by my Endocrinologist Iwas so happy to become part of the study, anything tohelp towards a cure for diabetes is well worth gettinginvolved with. TRIGR has been fantastic, the wholeteam is so helpful and if I had it over again I would notchange a thing. The study is well organized and Rosand Glenda are so knowledgeable.

Tiffany Williams

Life with diabetes has been a bit of a rollercoaster forme. I was diagnosed when I was about 12 and it tookuntil I was about 19 to get it all under control. Since

TRIGR in Australia

then I have worked very hard to keep my blood glucoselevel (BGL) within a normal range but it has been astruggle. I have recently gone on an insulin pump andmy BGL’s have improved immensely.

The Williams family

One of the biggest challenges of my life was to have ababy. It was all a bit scary but it worked out pretty well,although there were some hiccups along the way. Mydaughter Tiffany is now 2 and she is as bright, bubblyand beautiful as can be. It has been such a blessing tohave a healthy baby. I remember when I was first diag-nosed I was told that I would never be able to have chil-dren, what a long way we have come yet we still havefar to go. Hopefully with studies like this one the futurewill be much brighter for generations to come.

The story edited by Glenda Fraser,The Coordinator of Australia

The Moriarty family

We joined the TRIGR study last year in Sydney, Austra-lia following the birth of our second daughter KeiraGrace. Both my husband and his brother have type 1diabetes, diagnosed at 20 years and 5 years respec-tively. We appreciate being involved in this study be-cause we hope that our small contribution (and Keira’s!)will lead to more understanding of the causes of onsetfor this disease.

Keira 12 months

Keira had her 3 month visit at Sydney’s Westmead Chil-dren’s Hospital where she met the lovely TRIGR team –Dr Neville Howard, Glenda Fraser (Nurse Coordinator)and Ros Bongiorno (Nutrition Coordinator). I will neverforget the lovely conversation that Dr Howard and Keirahad, they cooed and chatted quite happily to each otherfor a few minutes, Dr Howard was a real natural and hada lovely rapport with our daughter. They were also veryhelpful on that visit as my husband managed to have ahypo while in their offices; it must have been the stressof Keira’s first blood test! Since then we have movedback to my homeland of New Zealand, but have beenfortunate enough to be able to continue with the TRIGRstudy, with Keira’s blood being collected here and couri-ered back to Australia. When Keira gets old enough tounderstand the blood tests and what they are for, weplan to make the ‘blood test day’ a special one for herwith lots of treats afterwards so that she looks forward tothem instead of dreading them!

Keira Moriarty

Regional centers of Czech Republic

Once upon a time, the dreaded beast Diabetes rav-aged the land and nothing could stop it. Audaciousknights from Finland led by Professor Hans Åkerblomraised a trial to put the menace to an end and asked

TRIGR in Czech Republic

their friends and fellows for help. Professor JanVavrinec was one of those answering their call andstepping to their side with a skilled army. In the veryheart of the Europe, in a beautiful land of forests,mountains and historical cities with only the sea miss-ing to call that piece of land the nature’s paradise, inthe Golden Town of Hundred Towers, the National co-ordinating center for the Czech branch of the TRIGRStudy was established. Soon after, Czech knightsjoined the war, heart and hand (privately nicknamingthe project „the reindeer milk miracle“ according to thecradle of the project and because questions aboutreindeer meat in the Dietary Interviews sounded veryexotic for Czech culture and were often talked about asa joke). Many families have allied with the study teamto help in research on diabetes prevention and to makesure that their children will be carefully followed. Alllived happily ever after… So far the fairy tale.

Our country joined the TRIGR study in Spring 2003with just one study center residing in Prague. Aftermeeting the necessary administrative preparations,our first TRIGR baby was born in August 2003. Duringthe following 2 years, more cooperating teams weresearched for throughout the whole country, and sixnew centers were established mostly in major regionalcities, in Brno, Olomouc, Usti nad Labem, Pilsen(Plzen), Ceske Budejovice and Zlin. This allowed us tocover entire country for recruitment purposes and toavoid missing as few eligible families as possible. Evenmore important, it made the follow-up more convenientfor the families already enrolled, especially from thepoint of view of the distance to the closest study center.

Prague, venue of our national coordinating center

The Czech Republic was invited to join the TRIGR pro-ject to facilitate recruitment and that was what we con-sidered to be our primary goal. A limited number ofchildren born in the Czech Republic fulfil the inclusioncriteria for the project (about 200 on an annual basis),so we developed a special recruitment hierarchy, con-sisting of several independent overlapping networks.The resulting structure we have named operationally“the multilayer snatching network”. The different layerswere related to specific individuals who learned toknow of the child during the pregnancy: parents andtheir lay friends, gynecologists, diabetologists, neona-tologists. All layers were supported by a serious of arti-cles in both professional and public newspapers andmagazines, by national web pages, a direct e-mail con-

tact to the national coordinating center and last but notleast, by the hotline phone available for all local TRIGRteams as well as families throughout the study (moreabout this later).

To ensure the highest level of medical care available,the study center visits take place in the hospitals of therespective local centers, which mostly belong to uni-versities. The families usually choose for the follow-upthe center closest to their home for the follow-up visits.Some of them have chosen Prague because of per-sonal ties there or because another diabetic familymember is followed there. Also, on their request, somefamilies living in distant mountain regions were grantedthe option of study visits to their family doctor and onlyannual visits at the local TRIGR center so they wouldnot have to travel too far with small babies.

On top of the regular phone calls for dietary interviewsand the Ancillary Study, during which not only the in-terview topics themselves are discussed but also eve-rything regarding the child’s health status, diet and de-velopment that the parents are interested in. We offeralso to our TRIGR families a “hotline“: a 24/7 non-stopmobile phone operated by an experienced paediatri-cian to help with any acute issues emerging. Thephone calls typically relate to “allowed” and “not al-lowed” food during the intervention period, infant colic,sudden fever or rash and acute illnesses in general.Sometimes, however, the requests are more challeng-ing, as we encourage the families to contact the teamevery time they feel we could be of any assistance.The most curious call received was from a father ask-ing for first aid advice for his 4-year old daughter, asister of a TRIGR child, who had eaten a worm. We arehappy that our families trust us so much that theyshare even small troubles.

To keep close contact with our families, we send notonly the regular TRIGR newsletters but also Christmascards with a small present. Of course we do not forgetto wish every child a happy birthday with a gift. Themost important thing, though, is the personal relation-ship we try to establish and develop with every family –the feeling of support, cooperation and availability weprovide.

Thanks to the above mentioned strategies we are veryproud that we enlisted 410 randomized and 164 eligiblechildren to the TRIGR study by the end of the recruit-ment period, thus being the European country with thesecond highest recruitment, right after the place of birthof the TRIGR idea, Finland. Considering the rathersmall Czech population (about 10 million people) andlower type 1 diabetes incidence here, we are veryhappy that we reached our goal. That would neverhave been possible without the heroic effort of all ourstaff and, most important, the enthusiasm of all the re-cruited families, whom I thank very much on behalf ofthe entire Czech coordinating team. Our Czech familiesshould feel proud of their substantial contribution to thesuccess of our research on the possible primary pre-vention of the type 1 diabetes.

Pavla MendlovaStudy DoctorCoordinator of Czech Republic