Type 2 Diabetes MellitusPhase 2MRBNCT03225209
Medically Reproducing Bariatric Surgery
A Phase 2 study testing OPTIFAST in people with Type 2 Diabetes Mellitus, run by Moahad S Dar at 1 site in United States.
Trial summary
Type 2 diabetes (DM2) is a chronic disease affecting 29 million Americans and a leading cause of blindness, kidney failure, and limb loss (Engelgau et al 2004). Roux-en-Y gastric bypass (RYGB) is the only intervention that leads to durable DM2 remission ~ 80% of the time (Mingrone et al 2012). Read more about this study
- Who is it for?
- Ages 25 to 70 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- OPTIFAST
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2018to 23 Oct 2018
- Phase
- Phase 2
- 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 25 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male or female
- age 25-70 years
- BMI > 30
- diagnosis of type 2 diabetes
- weight stable for 3 months
- hemoglobin A1C >7% and <10%
Show all 13Show fewer
- on Liraglutide
- on Metformin
- on Lantus
- interested in losing weight
- agreeable to regular visits per study protocol
- access to telephone and reliable transportation
- has a VAMC provider
Who cannot join
- age >70
- A1C <7% or >10%
- current use of prandial insulin
- current use of sulfonylurea or any other oral agent except for Metformin
- current sue of any other basal insulin except for Lantus
- pregnant
Show all 37Show fewer
- breast feeding
- prior history of pancreatitis
- prior history of gastroparesis
- history of thyroid cancer/multiple endocrine neoplasia/thyroid nodules/medullary thyroid cancer
- history of gallstones
- history of hyperoxaluria or calcium oxalate nephrolithiasis
- AST/ALT > 2 times the upper limit of normal
- current or past history of liver disease
- history of Roux-en-Y gastric bypass or gastric sleeve or any other bariatric procedure
- type 1 diabetes
- any gastrointestinal disease causing malabsorption
- unwilling or unable to complete scheduled testing
- thiazolidinedione use within past 6 months
- any serious and/or unstable medical, psychiatric, or other condition(s) that prevents the patient from providing informed consent or complying with the study
- organ transplantation or those on immunosuppressants
- chronic anticoagulation
- recent myocardial infarction, unstable angina, stroke, coronary artery bypass or transient ischemia attacks in the past 6 months
- chronic prednisone use
- peptic ulcer disease in past 6 months
- acute gastrointestinal disorders
- hepatitis
- cirrhosis
- GFR < 50
- deep vein thrombosis in the past 6 months
- bone fractures in the past 6 months
- lithium use
- active malignancy
- substance abuse
- unstable psychiatric condition
- history of suicidal ideation
- enrolled in another research study related to diet and/or physical activity
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Veteran Affairs, Greenville Health Care Center
Greenville, North Carolina, 27834
About this study
Type 2 diabetes (DM2) is a chronic disease affecting 29 million Americans and a leading cause of blindness, kidney failure, and limb loss (Engelgau et al 2004). Roux-en-Y gastric bypass (RYGB) is the only intervention that leads to durable DM2 remission ~ 80% of the time (Mingrone et al 2012). Yet, it's broad application is limited by cost, invasiveness, and clinical inertia. Medically reproducing RYGB would extend the benefit of disease remission to the vast majority of DM2 patients using a cheaper, less invasive and more palatable treatment approach. Although all of the mechanisms mediating DM2 remission are not known, it is widely accepted that RYGB induces caloric restriction and enhances meal-stimulated release of a gut-peptide called glucagon-like-peptide-1 (GLP-1) both of which improve glycemic control in type 2 diabetes (Dar et al 2012; Jackness 2013). Caloric restriction can be achieved using OPTIFAST which is a commercially available medical weight loss program that has demonstrated the ability to decrease weight and improve glycemic control (Kirschner et al; 1998). Enhanced meal-stimulated GLP-1 release can be achieved using Liraglutide an FDA-approved once daily GLP-1 analogue that improves glycemic control and induces weight loss.
The investigators hypothesize that adding OPTIFAST (caloric restriction) in suboptimally controlled DM2 patients on Liraglutide (enhanced meal stimulated GLP-1 release), Metformin and Lantus insulin will medically reproduce RYGB and lead to DM2 remission, weight loss, decreased medication intensity and improved health related quality of life.
Read the detailed description
This is a 24 week "proof of concept" study that will examine if adding "caloric restriction" (OPTIFAST) to "enhanced GLP-1 release" (Liraglutide) will lead to discontinuation of Lantus and Metformin. The primary outcome measure is change in glycemic control measured as hemoglobin A1C. Secondary outcome measures are change in weight, medication intensity and health related quality of life.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- OPTIFAST
- Keywords
- Roux-en-y gastric bypass, GLP-1, Liraglutide, OPTIFAST
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPTIFASTOther
OPTIFAST meal replacement includes shakes, bars and soups. These meal replacements will completely replace the subject's diet for the first 12 weeks of the study (baseline-week 12) followed by a gradual transition back to prepared meals over 6 weeks (week 13-18). Attempt will be made to reduce or eliminate Lantus and Metformin as long as glycemic control is maintained.
| Study group | Role | What they receive |
|---|---|---|
| OPTIFAST | Experimental | Subjects meeting inclusion criteria will be receive OPTIFAST meal replacement (MR) in the following manner:
WK1-WK12 (5 MR/DAY)
WK13-14 (4 MR/DAY)
WK 15 (3 MR/DAY)
WK 16 (2 MR/DAY)
WK 17-18 (1 MR/DAY)
WK 19-24 (No MR) Receives: Other: OPTIFAST |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glycemic control
Hemoglobin A1C (HbA1C) will be used to assess glycemic control during the study
Measured: Change in HbA1c from baseline at week 12 and week 24 will be measured
Secondary outcomes (5)
Change in Weight
Weight in kilograms will be used to assess weight change during the study
Measured: Change in weight in kilograms from baseline at week 12 and week 24 will be measured
Change in Medication intensity
Medication effect score (MES) will be used to assess medication intensity during the study
Measured: Change in MES from baseline at week 12 and week 24 will be measured
Change in Health Related Quality of Life (HRQOL)
Problem Areas in Diabetes Scale (PAID) is a well-validated measure used in clinical trials regarding diabetes and is a sensitive and specific measure of HRQOL.
Measured: Change in PAID from baseline at week 12, and week 24 will be measured
Change in Health Related Quality of Life
EQ-5D-5L is a highly sensitive 5-item health status measure with good performance in Veteran outpatients. It assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Measured: Change in EQ-5D-5L from baseline at week 12 and week 24 will be measured
Change in Physical activity
International Physical Activity Questionnaire (IPAQ) is a well validated tool to assess daily physical activity
Measured: Change in IPAQ from baseline at week 12 and week 24 will be measured
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start31 Jan 2018
- Primary completion23 Oct 2018
- Study completion23 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- "Proof of concept" study
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Moahad S Dar
- Sponsor type
- University, hospital or other
- Collaborators
- Société des Produits Nestlé (SPN), Durham VA Medical Center, East Carolina University
- Responsible party
- Sponsor-investigator, Moahad S Dar, East Carolina University
- Investigators
- Moahad Dar, MD, Principal investigator, Dept of Veteran Affairs
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03225209
- Sponsor's protocol ID
- 02050
- Acronym
- MRB
- Status last verified
- Jan 2020
- First submitted
- 5 Jul 2017
- Last updated
- 31 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB.
PubMed 12900694Dar MS, Chapman WH 3rd, Pender JR, Drake AJ 3rd, O'Brien K, Tanenberg RJ, Dohm GL, Pories WJ. GLP-1 response to a mixed meal: what happens 10 years after Roux-en-Y gastric bypass (RYGB)? Obes Surg. 2012 Jul;22(7):1077-83. doi: 10.1007/s11695-012-0624-1.
PubMed 22419108Engelgau MM, Geiss LS, Saaddine JB, Boyle JP, Benjamin SM, Gregg EW, Tierney EF, Rios-Burrows N, Mokdad AH, Ford ES, Imperatore G, Narayan KM. The evolving diabetes burden in the United States. Ann Intern Med. 2004 Jun 1;140(11):945-50. doi: 10.7326/0003-4819-140-11-200406010-00035.
PubMed 15172919Jackness C, Karmally W, Febres G, Conwell IM, Ahmed L, Bessler M, McMahon DJ, Korner J. Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and beta-cell Function in type 2 diabetic patients. Diabetes. 2013 Sep;62(9):3027-32. doi: 10.2337/db12-1762. Epub 2013 Apr 22.
PubMed 23610060Kirschner MA, Schneider G, Ertel NH, Gorman J. An eight-year experience with a very-low-calorie formula diet for control of major obesity. Int J Obes. 1988;12(1):69-80.
PubMed 3360564Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, Rubino F. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012 Apr 26;366(17):1577-85. doi: 10.1056/NEJMoa1200111. Epub 2012 Mar 26.
PubMed 22449317
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Medically Reproducing Bariatric Surgery
- ClinicalTrials.gov ID
- NCT03225209
- Acronym / sponsor ID
- MRB / 02050
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Roux-en-y gastric bypass, GLP-1, Liraglutide, OPTIFAST
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Moahad S DarUniversity, hospital or other
- Collaborators
- Société des Produits Nestlé (SPN), Durham VA Medical Center, East Carolina University
- Study start
- 31 Jan 2018 (actual)
- Primary completion
- 23 Oct 2018 (actual)
- Study completion
- 23 Oct 2018 (actual)
- First posted
- 21 Jul 2017 (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.
Type 2 diabetes (DM2) is a chronic disease affecting 29 million Americans and a leading cause of blindness, kidney failure, and limb loss (Engelgau et al 2004). Roux-en-Y gastric bypass (RYGB) is the only intervention that leads to durable DM2 remission ~ 80% of the time (Mingrone et al 2012). Yet, it's broad application is limited by cost, invasiveness, and clinical inertia. Medically reproducing RYGB would extend the benefit of disease remission to the vast majority of DM2 patients using a cheaper, less invasive and more palatable treatment approach. Although all of the mechanisms mediating DM2 remission are not known, it is widely accepted that RYGB induces caloric restriction and enhances meal-stimulated release of a gut-peptide called glucagon-like-peptide-1 (GLP-1) both of which improve glycemic control in type 2 diabetes (Dar et al 2012; Jackness 2013). Caloric restriction can be achieved using OPTIFAST which is a commercially available medical weight loss program that has demonstrated the ability to decrease weight and improve glycemic control (Kirschner et al; 1998). Enhanced meal-stimulated GLP-1 release can be achieved using Liraglutide an FDA-approved once daily GLP-1 analogue that improves glycemic control and induces weight loss.
The investigators hypothesize that adding OPTIFAST (caloric restriction) in suboptimally controlled DM2 patients on Liraglutide (enhanced meal stimulated GLP-1 release), Metformin and Lantus insulin will medically reproduce RYGB and lead to DM2 remission, weight loss, decreased medication intensity and improved health related quality of life.
Detailed description
This is a 24 week "proof of concept" study that will examine if adding "caloric restriction" (OPTIFAST) to "enhanced GLP-1 release" (Liraglutide) will lead to discontinuation of Lantus and Metformin. The primary outcome measure is change in glycemic control measured as hemoglobin A1C. Secondary outcome measures are change in weight, medication intensity and health related quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- "Proof of concept" study
| Arm | Type | Receives |
|---|---|---|
| OPTIFAST | Experimental | Other: OPTIFASTSubjects meeting inclusion criteria will be receive OPTIFAST meal replacement (MR) in the following manner: WK1-WK12 (5 MR/DAY) WK13-14 (4 MR/DAY) WK 15 (3 MR/DAY) WK 16 (2 MR/DAY) WK 17-18 (1 MR/DAY) WK 19-24 (No MR) |
Who may qualify
- Ages
- 25 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- male or female
- age 25-70 years
- BMI > 30
- diagnosis of type 2 diabetes
- weight stable for 3 months
Key exclusion criteria (37 listed)
- age >70
- A1C <7% or >10%
- current use of prandial insulin
- current use of sulfonylurea or any other oral agent except for Metformin
- current sue of any other basal insulin except for Lantus
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 |
|---|---|---|
| OPTIFASTOPTIFAST meal replacement includes shakes, bars and soups. These meal replacements will completely replace the subject's diet for the first 12 weeks of the study (baseline-week 12) followed by a gradual transition back to prepared meals over 6 weeks (week 13-18). Attempt will be made to reduce or eliminate Lantus and Metformin as long as glycemic control is maintained. | Other | OPTIFAST |
Primary outcome
Change in Glycemic control
Time frame: Change in HbA1c from baseline at week 12 and week 24 will be measured
Hemoglobin A1C (HbA1C) will be used to assess glycemic control during the study
5 secondary outcomes
Change in Weight
Time frame: Change in weight in kilograms from baseline at week 12 and week 24 will be measured
Change in Medication intensity
Time frame: Change in MES from baseline at week 12 and week 24 will be measured
Change in Health Related Quality of Life (HRQOL)
Time frame: Change in PAID from baseline at week 12, and week 24 will be measured
Change in Health Related Quality of Life
Time frame: Change in EQ-5D-5L from baseline at week 12 and week 24 will be measured
Change in Physical activity
Time frame: Change in IPAQ from baseline at week 12 and week 24 will be measured
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 31 Jan 2020.
- Background: PubMed 12900694Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB.
- Background: PubMed 22419108Dar MS, Chapman WH 3rd, Pender JR, Drake AJ 3rd, O'Brien K, Tanenberg RJ, Dohm GL, Pories WJ. GLP-1 response to a mixed meal: what happens 10 years after Roux-en-Y gastric bypass (RYGB)? Obes Surg. 2012 Jul;22(7):1077-83. doi: 10.1007/s11695-012-0624-1.
- Background: PubMed 15172919Engelgau MM, Geiss LS, Saaddine JB, Boyle JP, Benjamin SM, Gregg EW, Tierney EF, Rios-Burrows N, Mokdad AH, Ford ES, Imperatore G, Narayan KM. The evolving diabetes burden in the United States. Ann Intern Med. 2004 Jun 1;140(11):945-50. doi: 10.7326/0003-4819-140-11-200406010-00035.
- Background: PubMed 23610060Jackness C, Karmally W, Febres G, Conwell IM, Ahmed L, Bessler M, McMahon DJ, Korner J. Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and beta-cell Function in type 2 diabetic patients. Diabetes. 2013 Sep;62(9):3027-32. doi: 10.2337/db12-1762. Epub 2013 Apr 22.
- Background: PubMed 3360564Kirschner MA, Schneider G, Ertel NH, Gorman J. An eight-year experience with a very-low-calorie formula diet for control of major obesity. Int J Obes. 1988;12(1):69-80.
- Background: PubMed 22449317Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, Rubino F. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012 Apr 26;366(17):1577-85. doi: 10.1056/NEJMoa1200111. Epub 2012 Mar 26.
- Individual participant dataSharing planned: No
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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.
Moahad Dar, MD principal investigator
Dept of Veteran Affairs
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OPTIFAST in people with Type 2 Diabetes Mellitus, run by Moahad S Dar 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 13 inclusion and 37 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 31 Jan 2020. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Glycemic control (time frame: Change in HbA1c from baseline at week 12 and week 24 will be measured). 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 NCT03225209, which also lists 6 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 31 Jan 2020.