4081-DIA O.I. Handbook-v5med.stanford.edu/content/dam/sm/dped/documents/research/...because we might...

Oral Insulin for Prevention of Diabetesin Relatives at Risk for Type 1 Diabetes

Oral Insulin Handbook

4081-DIA O.I. Handbook-v5 2/22/07 3:35 PM Page 2

TYPE 1 DIABETES TRIALNET

Researchers in this study are part of a larger group called Type 1Diabetes TrialNet. TrialNet is an international network of centersdedicated to the study, prevention, and early treatment of type 1diabetes. We have 18 clinical centers in the United States, Canada,Europe, and Australia.

We are conducting studies to:• Learn more about the common risk factors among people who

get type 1 diabetes• Test treatments that could help delay or prevent the start of

type 1 diabetes• Test treatments that might help people keep producing their

own insulin when they are first diagnosed

TrialNet is jointly funded by:

To learn more about type 1 diabetes studies or to get a referral toa TrialNet study, call toll free 1-800-HALT-DM1 (1-800-425-8361).You can also learn more about TrialNet at www.diabetestrialnet.org.


Table of Contents

SECTION 1: Study Overview

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

a. Autoantibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

b. Oral insulin tried in earlier study . . . . . . . . . . . . . . . . . 4

3. Can I join the Oral Insulin Study? . . . . . . . . . . . . . . . . . . . . 5

a. Insulin autoantibodies . . . . . . . . . . . . . . . . . . . . . . . . . 5

b. Normal OGTT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

c. Informed consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

4. What will I do as a research volunteer in this study? . . . . . 6

a. Study capsules, study visits . . . . . . . . . . . . . . . . . . . . . . 6

b. Treatment group, control group . . . . . . . . . . . . . . . . . . . 6

c. Random assignment, double-masked . . . . . . . . . . . . . . . 6

d. Scheduling initial study visits. . . . . . . . . . . . . . . . . . . . . 6

5. “How long will this study last?” . . . . . . . . . . . . . . . . . . . . . 7

(Continued next page)


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Table of Contents (cont.)

SECTION 2: What to Expect While You Are in the Study

1. First Study Visit(s). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9a. IVGTT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2. Randomization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

3. Study Capsules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

a. How to take . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

b. Side effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

4. Three-Month Visit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

5. Follow-Up Visits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

a. Every 6 months . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

b. OGTT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

6. “How do I prepare for my study visits?”. . . . . . . . . . . . . . . . 15

a. Carbohydrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

b. Fast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

7. Schedule of Visits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

8. Watch for Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

9. Call Us Right Away If…. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19


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Section 1Study Overview


We are trying to find a way to delay or prevent type 1

diabetes. In this study, we are testing oral insulin (capsules of

insulin crystals). We will see if treatment with oral insulin

will result in fewer people developing diabetes compared to

the people in the study who do not receive oral insulin.

In the Natural History Study, you had blood tests that show

you are at risk for type 1 diabetes. This does not mean that

you will definitely develop diabetes. But we know that you

are at higher risk. We’re inviting you to join this study.

After you read this handbook, we will talk with you about the

study and answer your questions. We will ask you to take a

survey to make sure we’ve explained everything clearly. We

will then ask you to sign a consent form if you decide you

want to join the study. As you make your decision:

• Ask questions. We are always available for questions

and to discuss your concerns.

• Talk about the study with your family doctor.

Your doctor is welcome to call us with questions.

• Talk to your family and friends.

• Take the time you need to make your decision.

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Section 1


BackgroundWhen the immune system attacks the body’s own cells, as it

does in type 1 diabetes, different types of autoantibodies are

formed. One of these is insulin autoantibodies. There are

others. We can detect autoantibodies linked to diabetes up to

10 years before diabetes develops.

There is some evidence that if a person eats the same protein

that the immune system is reacting to, the immune system

will stop its attack. This was tried in an earlier prevention

trial in people at risk of diabetes. Half the people took a

capsule of insulin crystals every day. The others took capsules

with no insulin.

A similar number of people in both groups developed

diabetes. But in certain people—those with high levels of

insulin autoantibodies—oral insulin may have had an effect.

This new study is being done to see if oral insulin clearly

delays diabetes in people with similar test results. We are also

enrolling people with slightly different test results to gather

helpful information for future studies.

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Can I join the Oral Insulin Study?To be able to join the Oral Insulin Study, you must:

1. Have autoantibodies.The blood tests you had as part of the Natural History Study

showed that you have insulin autoantibodies. You must also

have at least one other type of autoantibody linked to diabetes.

2. Have a normal result on a recent oral glucose tolerance test (OGTT).You had an OGTT in the Natural History Study. If you had

the OGTT more than a month ago, you’ll need to have

another test before you can join this study.

3. Give informed consent.You can read this handbook.

You will need to take a survey so we can be sure that we

have explained everything clearly.

You will need to read and sign the Informed Consent.

4. Schedule your first Oral Insulin Study visit.The first visit should be as soon as possible after your OGTT,

because we might need to repeat a test. The repeat test has to

be done within 7 weeks of your OGTT.

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What will I do as a research volunteerin this study?If you join this study, you are agreeing to:

• Take one study capsule a day

• Come in for study visits, which include blood tests

Study MedicationHalf of the people in this study will get capsules filled with

insulin crystals. This is the treatment group.

The other half will get capsules filled with crystals that are

not insulin. A study medication that looks like the real thing

but does not have any active ingredients is called a placebo.

The people getting the placebo capsules are the control group.

You can’t choose which group you will be in. A computer will

put you in one of two groups. It’s by chance, like the flip of a

coin. This is called random assignment, or randomization.

This study is double-masked. While the study is on-going,

neither you nor your study team will know if you’re in the

treatment group or the control group. At the end of the

study, you will be able to find out what group you were in.

As a research volunteer, you can decide to stop being in this

study at any time. We hope that you will stay in the study.

You will be helping us learn more about preventing diabetes.6

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How long will this study last?This study started in 2007. We expect it will run until 2014 or

2015, or a few years longer if needed. We want to see if there

is a clear difference in the number of people who develop

diabetes in one group or the other (treatment or control). We

will need to follow people in the study for a number of years

before any differences will become clear.

At regular times during the study, a group of experts who are

not doing the actual study will look at the information being

collected. If these experts feel that it’s not safe to continue the

study, the study will be changed or stopped. If it becomes

clear that oral insulin does delay diabetes, the study will be

stopped, and everyone in the study will be told the results.

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Section 2What to expect whileyou are in the study


First Study Visit(s)When: Soon after your OGTT

Before you come: See page 15

Appointment Time: Early in the morning

Allow: 2 hours

What: - Physical exam

- IVGTT and other blood tests

- Urine pregnancy test

Part 1: Health ChecksWe will ask you about your health and your family’s health,

and about your diet and exercise habits.

We will do a physical exam.

We will need to do a urine pregnancy test on women and

girls of reproductive age. (If you become pregnant during

the study, you will have to stop taking the capsules.)

Part 2: IVGTT We want to find out how much insulin your body is making.

We will do this by giving glucose directly into your bloodstream.

Your body will respond by producing insulin. This test is

called an intravenous glucose tolerance test (IVGTT).

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Test Prep• For children, we offer a numbing cream. It’s put on the skin

30-60 minutes before the test. (Adults can ask for this, too.)

• We will insert a needle into a vein in your arm or hand. We

remove the needle, leaving a small plastic tube in your vein.

This is called an intravenous (IV) line. We draw all the

blood samples from this line.

• We will insert another IV line in your other arm or hand.

We will inject glucose into this line. (Some study teams use

only one IV line for both drawing blood samples and

injecting glucose.)

The Test • The whole test takes 20 minutes.

• We draw two samples of blood at the beginning of the test.

• We then inject glucose into your vein. (When the glucose is

injected, some people feel flushed and hot. This is a normal

reaction that will last only a minute.)

• We draw five samples of blood over the next 10 minutes.

We draw a total of 2 tablespoons of blood.

• We will also draw samples for autoantibodies, and for

future studies if you agreed to this.

The ResultsWe will get the test results in 1 to 2 weeks.

• If the results show that you are making a normal amount

of insulin, you can be in the study.

• If the results show that you are not making a normal

amount of insulin:

- You will need to come in for another visit before you are

randomized.

- We will do a second IVGTT to confirm the first result.

- About a third of the people in this study will need a

second IVGTT.


RandomizationWhen: Within 7 weeks of your OGTT

We will have a computer assign you to a study group.

• You will get study capsules.

• You should start taking the capsules the next morning.

Study CapsulesTake one study capsule a day, before breakfast.

• Swallow the capsule whole.

• For a child who can’t swallow capsules, open the capsule

and mix the contents in a soft food you know your child

will eat, such as applesauce, pudding, or yogurt.

It’s very important that you take one capsule every day.

• If you forget to take a capsule in the morning, take it before

lunch or dinner. If you miss a whole day, take just one

capsule the next day, as usual.

Save your empty bottles. Bring all bottles, empty and full,

to all of your visits.

Side EffectsIn the earlier study of oral insulin, no one reported any side

effects from taking the capsules.

You may know that injected insulin can cause low blood

glucose. Insulin taken by mouth does not cause low blood

glucose. Insulin is a protein. Once it’s digested in the

stomach, it can’t lower blood glucose. That’s why people with

diabetes have to take insulin by injection, not by mouth.

You will not get low blood glucose from taking the

study capsules.

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Three-Month VisitWhen: 3 months after you start taking the capsules

Appointment Time: Flexible

Allow: 1 hour

What: - Blood draw


Bring: Study bottles, empty or full.

We will draw blood for:

• A1c (shows average blood glucose levels over the past

2-3 months)

• Autoantibodies

• Samples to store for future studies, if you agreed to this


Follow-up VisitsWhen: Every 6 months

Before you come: See page 15

Appointment Time: Early in the morning

Allow: 3 to 4 hours

What: - OGTT and other blood tests


- Height, weight, blood pressure, and waist size

- Physical exam (done every other visit)

Oral Glucose Tolerance Test (OGTT)You had an OGTT in the Natural History Study. The result

was normal. Your body produced enough insulin to cover the

amount of glucose you would get in a large meal. We will do

this test every six months during this study to see if you’re

developing diabetes.

Test PrepAs in the IVGTT, we will put an IV line in a vein in your hand

or arm. We will take all the blood samples from this line.

You can have a numbing cream before the IV line is placed.

The Test • We will draw a blood sample at the beginning of the test.

• You will drink about a cup (less for children) of a very

sweet drink. You have to drink it all in 5 minutes. Some

people may feel sick to their stomachs (nauseated) when

they drink this.

• We will draw blood samples for 2 hours after you drink

the glucose.

• You will need to sit quietly or rest in bed during the test.

ResultsWe will get the results in 1 to 2 weeks. Sometimes the result

isn’t clear, and we will ask you to come in for another OGTT.

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Other Blood TestsBlood will be drawn for these other tests from the IV line

that’s in place for the OGTT.

• A1c (shows average blood glucose levels over the past

2-3 months)

• Autoantibodies

• Samples to be stored for future studies, if you agreed to this

In a small number of adults 18 years and older who weigh at

least 110 pounds (50 kilograms), we will take an extra sample

of blood of up to 2 tablespoons. We will use this sample to

help us make sure that the test results are accurate.

PhysicalsThe only difference between the half-year visits and the

full-year visits is the physical exam.

• Half-year visits

- Height, weight, blood pressure, and waist size

• Full-year visits

- A more complete physical exam

- Questions about your diet and exercise habits

Phone CallsWe will contact you between visits to check on you and make

sure you’re taking the study capsules.


How do I prepare for my study visits?For the study visits that include an intravenous glucosetolerance test (IVGTT) or an oral glucose tolerance test (OGTT):

Call us if you’re taking any prescription or over-the-counter medicine that you haven’t already told us about.Some medicines may change the test results.

Be sure to eat plenty of carbohydrate.Eat at least 150 grams of carbohydrate (starches and sugars)a day for at least three days before the test. Most adults andchildren eat 150 grams or more in a usual day, so this willprobably not mean a new diet for you or your child. Eatingmore than 150 grams of carbohydrate is OK. Foods withcarbohydrate include:

Grains: breads, pasta, crackers, cereals (hot and cold)BeansStarchy vegetables: potatoes, peas, cornFruit: fresh, canned, dried, juicesMilk: whole, 2%, 1%, non-fat, chocolate, yogurtSweets: candy, cookies, cakes, pies, regular sodas

Each of these has about 15 grams of carbohydrate:

• 1 slice of bread

• 6 crackers

• 1/2 cup pasta

• 1/3 cup rice

• 1 cup low-fat milk

• 1 medium apple

Meats and non-starchy vegetables (leafy greens, broccoli)have little or no carbohydrate. You can have these foods inthe amounts that you normally eat.

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Drink plenty of water the day before and the day ofthe test.It will be easier for us to do your test.

Have no food or drink other than water for 10 hoursbefore your test.This includes:

• No coffee or tea

• No alcohol

• No diet sodas or sugar-free gum. Even though these have no

calories, the flavor can prompt your body to make insulin,

and this may change the test results.

Also:

• Don’t use tobacco (smoking or chewing) or nicotine

replacement products.

• Don’t exercise.

• Get a good night’s sleep before the test.

- Don’t schedule the test for the morning after you work

a night shift.


Schedule of Visits

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NaturalHistoryStudy

OralInsulin,

first visit

Random-ization

3mo

6mo

9mo

1yr

15mo

18mo

21mo

2yrs

Every3

months

OGTT X X X X X

IVGTT X X(if needed)

Other bloodtests

X X(if needed) X X X X X

Urinepregnancy

testX X X X X X

Physicalexam

X X X

Bodymeasure-

mentsX X X

Phone call X X X X


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Watch for DiabetesSome people in this study will develop diabetes. We test youfor diabetes every six months. If you develop diabetes, we willprobably catch it at an early stage, before you have symptoms.This is one of the benefits of being on this study.

Still, be aware of the symptoms:

• Often thirsty

• Needs to go to the bathroom (urinate) a lot

• Tired

• Losing weight without trying

In addition, in a younger child:

• Sleeping more than usual

• More cranky than usual

• Wetting the bed when he or she used to stay dry at night

• Flu-like symptoms, including fever

If you think you might have diabetes, call us right away. Don’t wait until your next study visit or study phone call totell us. If you have symptoms of diabetes, we will schedulean extra visit right away. You should also talk with yourregular doctor.

• It is better for your health to be diagnosed as early as possible.

• It is very important to the success of the study that we do

these tests.

If your regular doctor or another doctor outside of TrialNettells you that you have diabetes:

• Tell the doctor that you are in a research study.

• Ask the doctor to call the study site right away. The study

site number is answered 24 hours a day. We will want to get

as much information as possible about your diagnosis.

If you develop diabetes, we will tell you about other researchstudies that might be open to you.


Call Us Right Away If…You have symptoms of diabetes. (See page 18)

• You have any questions or concerns about the study or

the capsules.

• You are having any problem taking the study capsules.

• You lose the study capsules. We will send you more

study capsules.

• You don’t want to be in the study any longer.

- You or your child are always free to stop being in the study.

Your future medical care will not be affected in any way.

- Please keep coming to the 6-month visits even if you stop

taking the study capsules. We want to monitor you for

possible development of diabetes.

In Case of Emergency: Call 9-1-1Life-threatening emergencies should not arise from the study.

• In the event of a life-threatening emergency,

ALWAYS CALL 9-1-1.

• Get medical attention right away rather than calling your

study team.

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TrialNet is a network of diabetes centers dedicated to the study, prevention, and earlytreatment of type 1 diabetes.

February, 2007


4081-DIA O.I. Handbook-v5med.stanford.edu/content/dam/sm/dped/documents/research/...because we might...

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