Diabetes Mellitus, Type 2CutDM-HypoNCT03814694
Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes. The Hypo-energetic Study
A study testing CRHP Diet and CD Diet in people with Diabetes Mellitus, Type 2 and Overweight and Obesity, run by Bispebjerg Hospital at 1 site in Denmark.
Trial summary
Scientific evidence for the dietary treatment of type 2 diabetes (T2D) is insufficient, which is why the investigators aim to reform dietary recommendation to the overweight or obese patient with type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2, Overweight and Obesity
- What is being tested?
- CRHP Diet and CD Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteDenmark
- Study dates
- 29 Jan 2019to 30 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes with HbA1c between 48 mmol/mol and 97 mmol/mol with or without metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors
- Overweight or obesity with BMI ≥ 25 kg/m2 and desired weight loss
- Non-smokers for > 1 year
- Willingness to abstain from alcohol for 6 weeks
- Hemoglobin > 7 mmol/L for men and > 6 mmol/L for women
- Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2
Who cannot join
- Critical illness as evaluated by the principal investigator
- Systemic corticosteroid treatment, e.g. prednisolone
- Reported or journalized severe food allergy or intolerance
- Reported or journalized severe gut disease e.g. Crohn's disease, Coeliac disease etc.
- Reported or journalized alcohol dependence syndrome
- Injectable diabetes medication, including insulin and GLP-1 analogues
Show all 12Show fewer
- Sulfonylureas (SUs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, unless discontinuation is possible, in which case a 2-month wash-out is mandatory
- Repeated fasting plasma glucose > 13.3 mmol/L
- Urine albumin / creatinine ratio > 300 mg/g
- Lactation, pregnancy or planning of pregnancy during the study
- Inability, physically or mentally, to comply with the procedures required by the study protocol, as evaluated by the principal investigator
- Presently participating in other clinical trials
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes; Mechanisms of Effective Therapy of Diabetes by Selective Choice of Macronutrients. The Hypo-energetic Study.
Scientific evidence for the dietary treatment of type 2 diabetes (T2D) is insufficient, which is why the investigators aim to reform dietary recommendation to the overweight or obese patient with type 2 diabetes. This clinical study will examine the effect of a highly controlled hypo-energetic carbohydrate-reduced high-protein (CRHP) diet intervention under caloric restriction-induced body weight loss as a treatment modality in T2D. The investigators hypothesize that this intervention compared to the conventional diabetes (CD) diet with similar loss in body weight improves metabolic control and cardiovascular risk profile in T2D by:
- Reducing diurnal and postprandial glycaemia, thereby facilitating a significant reduction in HbA1c
- Reducing ectopic lipid deposits in liver, muscle and pancreas
- Improving lipid profile towards a less atherogenic profile
- Improving metabolic actions of insulin, through increased sensitivity and β-cell function
- Reducing diurnal blood pressure with no adverse effect on heart rate variability
Read the detailed description
The present study will be performed as a 6-week randomized fully controlled feeding study, which will address the effect of the hypo-energetic CRHP diet compared with the hypo-energetic CD diet with the macronutrient composition currently recommended to patients with T2D combined with a caloric restriction-induced 5-7% body weight loss on T2D. The study includes n=80 T2D patients.
Measurements include fasting blood samples every 2 weeks during the 6 weeks of the study. Additionally, larger measurement programs will be undertaken at baseline and after 6 weeks, including MRi/s for liver, pancreas and muscle fat content and visceral and subcutaneous adipose tissue; DXA scans for body composition; oral glucose tolerance tests (OGTT); continuous glucose monitoring (CGM); diurnal blood pressure and holter recording. Questionnaires of health-related quality of life, level of physical activity and satiety by visual analogue scale will be performed at baseline and week 6 as well as fecal and diurnal urine sampling.
To ensure a similar body weight loss between intervention groups as well as participants, aimed at 5-7%, caloric intake during the 6 weeks of the study will be hypo-energetic adjusted for each participant according to estimated daily total energy expenditure (TEE). A calculation requiring sex, age, weight and height will be performed to estimate resting energy expenditure (REE), which multiplied with the participant's physical activity level (PAL) will estimate TEE, and thus with an initial caloric deficit of 5% determine the caloric content in the hypo-energetic diet for each participant. Additionally, participants will be weighed twice a week and caloric content adjusted accordingly to ensure a controlled body weight loss.
It is important to recognize that the CRHP diet and the CD diet principally do not differ in the quality of carbohydrate and protein. Thus, this study is unable to address a potential benefit of changes in quality of carbohydrate; however, both diet interventions exhibit a relatively low glycemic index of maximum 55.
Until week 6 diets will be prepared and distributed from the research kitchen of the Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark, to optimize compliance and adherence to the prescribed diet. Following this period and again after approximately 3 months participants will be invited to group sessions with dietician guidance on how to sustain their body weight loss and continue with their assigned diet. A follow-up visit at week 30 will include a blood sample, a spot urine sample and body weight measurement.
- Conditions
- Diabetes Mellitus, Type 2, Overweight and Obesity
- Being tested
- CRHP Diet, CD Diet
- Keywords
- Weight Loss, Diet, Carbohydrate-Restricted, Diet, High-Protein, Insulin Resistance, Non-alcoholic Fatty Liver Disease, Metabolic Syndrome
- Medical subject headings
- Diabetes Mellitus, Type 2, Overweight, Obesity, Weight Loss, Insulin Resistance, Non-alcoholic Fatty Liver Disease, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CRHP DietDietary supplement
Dietary macronutrient composition of 30 E% from carbohydrate, 30 E% from protein and 40 E% from fat
CD DietDietary supplement
Dietary macronutrient composition of 50 E% from carbohydrate, 17 E% from protein and 33 E% from fat
| Study group | Role | What they receive |
|---|---|---|
| CRHP Diet | Experimental | Hypo-energetic carbohydrate-reduced high-protein (CRHP) dietary intervention with a controlled 5-7% loss in body weight. Receives: Dietary Supplement: CRHP Diet |
| CD Diet | Active comparator | Hypo-energetic conventional diabetes (CD) dietary intervention with a controlled 5-7% loss in body weight. Receives: Dietary Supplement: CD Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in glycated hemoglobin (HbA1c) during 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.
The change in HbA1c will be assessed during 6 weeks of fully provisioned hypo-energetic CRHP diet compared with hypo-energetic CD diet, while achieving concurrent body weight loss of 5-7 percent in both groups. Levels of HbA1c will be measured at baseline, week 2, 4, 5 and 6. HbA1c will be expressed in mmol/mol.
Measured: 6 weeks
Secondary outcomes (2)
Change in hepatic fat content after 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.
Hepatic fat content will be assessed by magnetic resonance spectroscopy (MRs) at baseline and week 6.
Measured: 6 weeks
Change in fasting plasma triglycerides during 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.
Levels of triglycerides will be measured from fasting at baseline, week 2, 4, 5 and 6. Triglycerides will be expressed in mmol/L.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start29 Jan 2019
- Primary completion22 Jul 2020
- Study completion30 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bispebjerg Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen, University of Aarhus, The Danish Dairy Research Foundation, Denmark, Arla Foods
- Responsible party
- Principal investigator, Mads N Thomsen, Bispebjerg Hospital
- Investigators
- Steen B Haugaard, Professor, Principal investigator, Dept. of Endocrinology, Copenhagen University Hospital Bispebjerg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03814694
- Sponsor's protocol ID
- CUTDM-HYPO
- Acronym
- CutDM-Hypo
- Status last verified
- Jan 2021
- First submitted
- 8 Jan 2019
- Last updated
- 27 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) may be shared by request to the corresponding author in accordance with the Danish Data Protection Agency.
Publications
Thomsen MN, Skytte MJ, Samkani A, Weber P, Fenger M, Frystyk J, Hansen E, Holst JJ, Madsbad S, Magkos F, Thomsen HS, Walzem RL, Haugaard SB, Krarup T. Replacing dietary carbohydrate with protein and fat improves lipoprotein subclass profile and liver fat in type 2 diabetes independent of body weight: evidence from 2 randomized controlled trials. Am J Clin Nutr. 2025 Feb;121(2):224-231. doi: 10.1016/j.ajcnut.2024.11.030. Epub 2024 Nov 29.
PubMed 39617302Jensen NJ, Wodschow HZ, Skytte MJ, Samkani A, Astrup A, Frystyk J, Hartmann B, Holst JJ, Larsen TM, Madsbad S, Magkos F, Miskowiak KW, Haugaard SB, Krarup T, Rungby J, Thomsen MN. Weight-loss induced by carbohydrate restriction does not negatively affect health-related quality of life and cognition in people with type 2 diabetes: A randomised controlled trial. Clin Nutr. 2022 Jul;41(7):1605-1612. doi: 10.1016/j.clnu.2022.05.005. Epub 2022 May 18.
PubMed 35679680Thomsen MN, Skytte MJ, Samkani A, Carl MH, Weber P, Astrup A, Chabanova E, Fenger M, Frystyk J, Hartmann B, Holst JJ, Larsen TM, Madsbad S, Magkos F, Thomsen HS, Haugaard SB, Krarup T. Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial. Diabetologia. 2022 Mar;65(3):506-517. doi: 10.1007/s00125-021-05628-8. Epub 2022 Jan 7.
PubMed 34993571
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes; Mechanisms of Effective Therapy of Diabetes by Selective Choice of Macronutrients. The Hypo-energetic Study.
- ClinicalTrials.gov ID
- NCT03814694
- Acronym / sponsor ID
- CutDM-Hypo / CUTDM-HYPO
- Conditions
- Diabetes Mellitus, Type 2, Overweight and Obesity
- Keywords
- Weight Loss, Diet, Carbohydrate-Restricted, Diet, High-Protein, Insulin Resistance, Non-alcoholic Fatty Liver Disease, Metabolic Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Bispebjerg HospitalUniversity, hospital or other
- Collaborators
- University of Copenhagen, University of Aarhus, The Danish Dairy Research Foundation, Denmark, Arla Foods
- Study start
- 29 Jan 2019 (actual)
- Primary completion
- 22 Jul 2020 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 24 Jan 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.
Scientific evidence for the dietary treatment of type 2 diabetes (T2D) is insufficient, which is why the investigators aim to reform dietary recommendation to the overweight or obese patient with type 2 diabetes. This clinical study will examine the effect of a highly controlled hypo-energetic carbohydrate-reduced high-protein (CRHP) diet intervention under caloric restriction-induced body weight loss as a treatment modality in T2D. The investigators hypothesize that this intervention compared to the conventional diabetes (CD) diet with similar loss in body weight improves metabolic control and cardiovascular risk profile in T2D by:
- Reducing diurnal and postprandial glycaemia, thereby facilitating a significant reduction in HbA1c
- Reducing ectopic lipid deposits in liver, muscle and pancreas
- Improving lipid profile towards a less atherogenic profile
- Improving metabolic actions of insulin, through increased sensitivity and β-cell function
- Reducing diurnal blood pressure with no adverse effect on heart rate variability
Detailed description
The present study will be performed as a 6-week randomized fully controlled feeding study, which will address the effect of the hypo-energetic CRHP diet compared with the hypo-energetic CD diet with the macronutrient composition currently recommended to patients with T2D combined with a caloric restriction-induced 5-7% body weight loss on T2D. The study includes n=80 T2D patients.
Measurements include fasting blood samples every 2 weeks during the 6 weeks of the study. Additionally, larger measurement programs will be undertaken at baseline and after 6 weeks, including MRi/s for liver, pancreas and muscle fat content and visceral and subcutaneous adipose tissue; DXA scans for body composition; oral glucose tolerance tests (OGTT); continuous glucose monitoring (CGM); diurnal blood pressure and holter recording. Questionnaires of health-related quality of life, level of physical activity and satiety by visual analogue scale will be performed at baseline and week 6 as well as fecal and diurnal urine sampling.
To ensure a similar body weight loss between intervention groups as well as participants, aimed at 5-7%, caloric intake during the 6 weeks of the study will be hypo-energetic adjusted for each participant according to estimated daily total energy expenditure (TEE). A calculation requiring sex, age, weight and height will be performed to estimate resting energy expenditure (REE), which multiplied with the participant's physical activity level (PAL) will estimate TEE, and thus with an initial caloric deficit of 5% determine the caloric content in the hypo-energetic diet for each participant. Additionally, participants will be weighed twice a week and caloric content adjusted accordingly to ensure a controlled body weight loss.
It is important to recognize that the CRHP diet and the CD diet principally do not differ in the quality of carbohydrate and protein. Thus, this study is unable to address a potential benefit of changes in quality of carbohydrate; however, both diet interventions exhibit a relatively low glycemic index of maximum 55.
Until week 6 diets will be prepared and distributed from the research kitchen of the Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark, to optimize compliance and adherence to the prescribed diet. Following this period and again after approximately 3 months participants will be invited to group sessions with dietician guidance on how to sustain their body weight loss and continue with their assigned diet. A follow-up visit at week 30 will include a blood sample, a spot urine sample and body weight measurement.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CRHP Diet | Experimental | Dietary Supplement: CRHP DietHypo-energetic carbohydrate-reduced high-protein (CRHP) dietary intervention with a controlled 5-7% loss in body weight. |
| CD Diet | Active comparator | Dietary Supplement: CD DietHypo-energetic conventional diabetes (CD) dietary intervention with a controlled 5-7% loss in body weight. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Type 2 diabetes with HbA1c between 48 mmol/mol and 97 mmol/mol with or without metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors
- Overweight or obesity with BMI ≥ 25 kg/m2 and desired weight loss
- Non-smokers for > 1 year
- Willingness to abstain from alcohol for 6 weeks
- Hemoglobin > 7 mmol/L for men and > 6 mmol/L for women
Key exclusion criteria (12 listed)
- Critical illness as evaluated by the principal investigator
- Systemic corticosteroid treatment, e.g. prednisolone
- Reported or journalized severe food allergy or intolerance
- Reported or journalized severe gut disease e.g. Crohn's disease, Coeliac disease etc.
- Reported or journalized alcohol dependence syndrome
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 |
|---|---|---|
| CRHP DietDietary macronutrient composition of 30 E% from carbohydrate, 30 E% from protein and 40 E% from fat | Dietary supplement | CRHP Diet |
| CD DietDietary macronutrient composition of 50 E% from carbohydrate, 17 E% from protein and 33 E% from fat | Dietary supplement | CD Diet |
Primary outcome
Change in glycated hemoglobin (HbA1c) during 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.
Time frame: 6 weeks
The change in HbA1c will be assessed during 6 weeks of fully provisioned hypo-energetic CRHP diet compared with hypo-energetic CD diet, while achieving concurrent body weight loss of 5-7 percent in both groups. Levels of HbA1c will be measured at baseline, week 2, 4, 5 and 6. HbA1c will be expressed in mmol/mol.
2 secondary outcomes
Change in hepatic fat content after 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.
Time frame: 6 weeks
Change in fasting plasma triglycerides during 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
- Derived from this study: PubMed 39617302Thomsen MN, Skytte MJ, Samkani A, Weber P, Fenger M, Frystyk J, Hansen E, Holst JJ, Madsbad S, Magkos F, Thomsen HS, Walzem RL, Haugaard SB, Krarup T. Replacing dietary carbohydrate with protein and fat improves lipoprotein subclass profile and liver fat in type 2 diabetes independent of body weight: evidence from 2 randomized controlled trials. Am J Clin Nutr. 2025 Feb;121(2):224-231. doi: 10.1016/j.ajcnut.2024.11.030. Epub 2024 Nov 29.
- Derived from this study: PubMed 35679680Jensen NJ, Wodschow HZ, Skytte MJ, Samkani A, Astrup A, Frystyk J, Hartmann B, Holst JJ, Larsen TM, Madsbad S, Magkos F, Miskowiak KW, Haugaard SB, Krarup T, Rungby J, Thomsen MN. Weight-loss induced by carbohydrate restriction does not negatively affect health-related quality of life and cognition in people with type 2 diabetes: A randomised controlled trial. Clin Nutr. 2022 Jul;41(7):1605-1612. doi: 10.1016/j.clnu.2022.05.005. Epub 2022 May 18.
- Derived from this study: PubMed 34993571Thomsen MN, Skytte MJ, Samkani A, Carl MH, Weber P, Astrup A, Chabanova E, Fenger M, Frystyk J, Hartmann B, Holst JJ, Larsen TM, Madsbad S, Magkos F, Thomsen HS, Haugaard SB, Krarup T. Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial. Diabetologia. 2022 Mar;65(3):506-517. doi: 10.1007/s00125-021-05628-8. Epub 2022 Jan 7.
- Individual participant dataSharing planned: No. Individual participant data (IPD) may be shared by request to the corresponding author in accordance with the Danish Data Protection Agency.
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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. This study is not recruiting at the moment.
Steen B Haugaard, Professor principal investigator
Dept. of Endocrinology, Copenhagen University Hospital Bispebjerg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CRHP Diet and CD Diet in people with Diabetes Mellitus, Type 2 and Overweight and Obesity, run by Bispebjerg Hospital at 1 site in Denmark.
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 6 inclusion and 12 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: finished, as of the sponsor's last update on 27 Jan 2021. 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 Denmark. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in glycated hemoglobin (HbA1c) during 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet. (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03814694, which also lists 3 linked publications.
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 27 Jan 2021.