Type1diabetesNCT04200391
Very Low Carbohydrate Diets and Glucagon Response in T1DM
A study testing Very low carbohydrate diet in people with Type1diabetes, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Despite major technological advances, management of type one diabetes mellitus (T1D) remains suboptimal, putting millions of people at risk for immediate and long-term complications. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Type1diabetes
- What is being tested?
- Very low carbohydrate diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2020to 31 Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males and females with T1D for at least 1 year
- Age 18 to 40 years
- Tanner stage ≥ IV
- BMI 18.5-35 kg/m2
- Stable glycemic control (HbA1c 6.5-9%)
- Use of a continuous glucose monitor (CGM)
- Use of an insulin pump
- Attendance of at least 1 diabetes care visit over the past 12 months (including virtual)
Who cannot join
- Ketoacidosis or severe hypoglycemia with seizure or coma in the past 6 months
- Dietary restrictions or intolerances that are incompatible with the planned food deliveries, e.g. celiac disease, gastroparesis, certain food allergies
- Following a weight-loss or otherwise restrictive diet
- Vigorous exercise >2 hours on >3 days a week
- History of an eating disorder or at risk for eating disorder, assessed by the Eating Disorders Diagnostic Scale (EDDS)
- Major medical illness or use of medications other than insulin and metformin that could interfere with metabolic or glycemic variables
Show all 14Show fewer
- Significant psychiatric illness
- Smoking, use of recreational drugs, or excessive alcohol consumption
- Pregnancy or breastfeeding
- Anemia
- For participants who undergo MRI:
- Standard MRI exclusion criteria
- Irregular menses
- Use of psychotropic medication other than SSRIs or other mild antidepressant or anxiety medications (unless these medications are safe to be held for several days to allow for the acquisition of MRI data).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Belinda S Lennerz, 857-218-3896 ext. 8572183896, belinda.lennerz@childrens.harvard.edu
About this study
Official title: Glucagon Response in Patients With Type 1 Diabetes Mellitus Following a Very Low Carbohydrate
Despite major technological advances, management of type one diabetes mellitus (T1D) remains suboptimal, putting millions of people at risk for immediate and long-term complications. After meals, a mismatch between carbohydrate absorption rate and insulin action typically leads to alternating periods of hyper- and hypoglycemia. A conceptually promising approach to control both problems is dietary carbohydrate restriction to reduce postprandial blood glucose changes and insulin needs. In a prior survey study, the investigators documented exceptional glycemic control (HbA1c 5.67%) and low acute complication rates among 316 children and adults with T1D consuming a very-low-carbohydrate (VLC) diet. Despite these promising preliminary results, the use of VLC diets for T1D remain controversial, because of their restrictive nature and theoretical concerns regarding growth, ketoacidosis and hypoglycemia risks and efficiency of glucagon treatment for hypoglycemia. Glucagon is used as a rescue medication during severe hypoglycemia and increases blood glucose levels by mobilizing liver glycogen stores. If these stores are depleted during carbohydrate restriction, glucagon response may be inadequate and put individuals at risk for refractory hypoglycemia. A physiologic study has shown a blunted but still adequate response to glucagon in n=10 participants after following a VLCD for 1 week. Longer-term studies have not been done.
To test the hypotheses that glucagon response remains adequate while following a VLC diet in the longer term, the investigators will conduct a glucagon challenge in participants who are assigned to the VLC arm of a randomized-controlled feeding study in 32 young adults with T1D who will receive a VLC vs a standard diet for 12 weeks. After an overnight fast, twelve participants in the VLC arm will receive IV insulin to lower blood glucose levels to 60 mg/dL, followed by a glucagon injection and monitoring of blood glucose levels and other metabolic fuels.
- Conditions
- Type1diabetes
- Being tested
- Very low carbohydrate diet
- Keywords
- nutrition, very low carbohydrate diet, ketogenic diet, nutritional ketosis, glucagon, hypoglycemia, glycogen, ketosis, ketones
- Medical subject headings
- Hypoglycemia, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Very low carbohydrate dietOther
All meals will be delivered and participants will consume study foods exclusively. Participants will receive a fiber supplement with each meal as needed to promote digestive health, and a daily multi-vitamin, magnesium and omega-3 supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance.
The diet composition will be as follows: 5% carbohydrate, 75% fat, 20% protein.
| Study group | Role | What they receive |
|---|---|---|
| Very low carbohydrate diet | Experimental | Dietary Intervention, food delivery Receives: Other: Very low carbohydrate diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucagon treatment success, defined as an increase in glucose level to ≥ 70 mg/dL or an Increase of ≥ 20 mg/dL from glucose nadir within 30 minutes after receiving 1 mg glucagon IM
Point-of-care blood glucose levels will be measured pre-dose and every 5 minutes for 30 minutes and until BG is ≥ 70 mg/dL (whichever occurs later), then gradually spaced per MD orders to align with the rest of the labs
Measured: week 5-12 on the very low carbohydrate diet
Secondary outcomes (5)
Recovery from symptoms of hypoglycemia
Recovery from hypoglycemia symptoms will be assessed using a Hypoglycemia Symptoms Scale at baseline, when blood glucose is < 75 mg/dL, pre-dose, and at 15, 30, 45, 60, 75, and 90 minutes following administration of glucagon. The Hypoglycemia Symptoms Scale measures the intensity of 14 commonly experienced hypoglycemic symptoms on a scale from 0 (not present) to 6 (very intense). The higher the score, the more intense the hypoglycemia symptoms. The sum of each symptom score would yield a range of 0 to 84 (e.g., 14 x 6 = 84). The total score will be calculated as the sum of each symptom score and summarized at each time point.
Measured: week 5-12 on the very low carbohydrate diet
Time to achieve glucagon treatment success
The mean time from glucagon administration to blood glucose ≥ 70 mg/dL or an increase ≥ 20 mg/dL in blood glucose from nadir. Point-of-care blood glucose levels will be measured pre-dose and every 5 minutes for 30 minutes and until BG is ≥ 70 mg/dL (whichever occurs later), then gradually spaced per MD orders to align with the rest of the labs.
Measured: week 5-12 on the very low carbohydrate diet
Plasma levels of beta-hydroxybutyrate following glucagon administration
Levels will be measured at baseline, pre-dose, and at 10, 20, 30, 45, 60, and 90 minutes. Average levels at each time point, peak level, and area under the curve (AUC) will be reported.
Measured: week 5-12 on the very low carbohydrate diet
Plasma levels of free fatty acids following glucagon administration
Levels will be measured at baseline, pre-dose, 10, 20, 30, 45, 60, and 90 minutes. Average levels at each time point, peak level, and area under the curve (AUC) will be reported.
Measured: week 5-12 on the very low carbohydrate diet
Plasma glucose levels following glucagon administration
Levels will be measured at baseline, pre-dose, and at 10, 20, 30, 45, 60, and 90 minutes. Average levels at each time point, peak level, and area under the curve (AUC) will be reported.
Measured: week 5-12 on the very low carbohydrate diet
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start3 Jan 2020
- Primary completion31 Jul 2026 (estimated)
- Study completion31 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type1diabetesStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants will receive a very low carbohydrate diet for 12 weeks and undergo a glucagon challenge during weeks 5-12 to assess glycemic response.
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Belinda Lennerz, Boston Children's Hospital
- Investigators
- Belinda S Lennerz, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04200391
- Sponsor's protocol ID
- IRB-P00030039_3
- Status last verified
- Dec 2024
- First submitted
- 12 Dec 2019
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucagon Response in Patients With Type 1 Diabetes Mellitus Following a Very Low Carbohydrate
- ClinicalTrials.gov ID
- NCT04200391
- Acronym / sponsor ID
- IRB-P00030039_3
- Conditions
- Type1diabetes
- Keywords
- nutrition, very low carbohydrate diet, ketogenic diet, nutritional ketosis, glucagon, hypoglycemia, glycogen, ketosis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 3 Jan 2020 (actual)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 31 Jul 2026 (estimated)
- First posted
- 16 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite major technological advances, management of type one diabetes mellitus (T1D) remains suboptimal, putting millions of people at risk for immediate and long-term complications. After meals, a mismatch between carbohydrate absorption rate and insulin action typically leads to alternating periods of hyper- and hypoglycemia. A conceptually promising approach to control both problems is dietary carbohydrate restriction to reduce postprandial blood glucose changes and insulin needs. In a prior survey study, the investigators documented exceptional glycemic control (HbA1c 5.67%) and low acute complication rates among 316 children and adults with T1D consuming a very-low-carbohydrate (VLC) diet. Despite these promising preliminary results, the use of VLC diets for T1D remain controversial, because of their restrictive nature and theoretical concerns regarding growth, ketoacidosis and hypoglycemia risks and efficiency of glucagon treatment for hypoglycemia. Glucagon is used as a rescue medication during severe hypoglycemia and increases blood glucose levels by mobilizing liver glycogen stores. If these stores are depleted during carbohydrate restriction, glucagon response may be inadequate and put individuals at risk for refractory hypoglycemia. A physiologic study has shown a blunted but still adequate response to glucagon in n=10 participants after following a VLCD for 1 week. Longer-term studies have not been done.
To test the hypotheses that glucagon response remains adequate while following a VLC diet in the longer term, the investigators will conduct a glucagon challenge in participants who are assigned to the VLC arm of a randomized-controlled feeding study in 32 young adults with T1D who will receive a VLC vs a standard diet for 12 weeks. After an overnight fast, twelve participants in the VLC arm will receive IV insulin to lower blood glucose levels to 60 mg/dL, followed by a glucagon injection and monitoring of blood glucose levels and other metabolic fuels.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants will receive a very low carbohydrate diet for 12 weeks and undergo a glucagon challenge during weeks 5-12 to assess glycemic response.
| Arm | Type | Receives |
|---|---|---|
| Very low carbohydrate diet | Experimental | Other: Very low carbohydrate dietDietary Intervention, food delivery |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Males and females with T1D for at least 1 year
- Age 18 to 40 years
- Tanner stage ≥ IV
- BMI 18.5-35 kg/m2
- Stable glycemic control (HbA1c 6.5-9%)
Key exclusion criteria (14 listed)
- Ketoacidosis or severe hypoglycemia with seizure or coma in the past 6 months
- Dietary restrictions or intolerances that are incompatible with the planned food deliveries, e.g. celiac disease, gastroparesis, certain food allergies
- Following a weight-loss or otherwise restrictive diet
- Vigorous exercise >2 hours on >3 days a week
- History of an eating disorder or at risk for eating disorder, assessed by the Eating Disorders Diagnostic Scale (EDDS)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Very low carbohydrate dietAll meals will be delivered and participants will consume study foods exclusively. Participants will receive a fiber supplement with each meal as needed to promote digestive health, and a daily multi-vitamin, magnesium and omega-3 supplement to ascertain micronutrient sufficiency. Participants will be weighed at each study visit and the diet plan will be adjusted for satiety and weight-maintenance. The diet composition will be as follows: 5% carbohydrate, 75% fat, 20% protein. | Other | Very low carbohydrate diet |
Primary outcome
Glucagon treatment success, defined as an increase in glucose level to ≥ 70 mg/dL or an Increase of ≥ 20 mg/dL from glucose nadir within 30 minutes after receiving 1 mg glucagon IM
Time frame: week 5-12 on the very low carbohydrate diet
Point-of-care blood glucose levels will be measured pre-dose and every 5 minutes for 30 minutes and until BG is ≥ 70 mg/dL (whichever occurs later), then gradually spaced per MD orders to align with the rest of the labs
5 secondary outcomes
Recovery from symptoms of hypoglycemia
Time frame: week 5-12 on the very low carbohydrate diet
Time to achieve glucagon treatment success
Time frame: week 5-12 on the very low carbohydrate diet
Plasma levels of beta-hydroxybutyrate following glucagon administration
Time frame: week 5-12 on the very low carbohydrate diet
Plasma levels of free fatty acids following glucagon administration
Time frame: week 5-12 on the very low carbohydrate diet
Plasma glucose levels following glucagon administration
Time frame: week 5-12 on the very low carbohydrate diet
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Belinda S Lennerz principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Very low carbohydrate diet in people with Type1diabetes, run by Boston Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Belinda S Lennerz, MD, PhD (8572183896 ext. 6173557476, belinda.lennerz@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucagon treatment success, defined as an increase in glucose level to ≥ 70 mg/dL or an Increase of ≥ 20 mg/dL from glucose nadir within 30 minutes after receiving 1 mg glucagon IM (time frame: week 5-12 on the very low carbohydrate diet). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024; AzTrials last refreshed its copy on 26 Oct 2026.