PreDiabetesePREDICENCT03222765
Prevention of Microvascular Complications in Prediabetes e-PREDICE Study
A study of PreDiabetes, run by Evidem Consultores SL at 1 site in Spain.
Trial summary
Background: A significant proportion of pre-diabetics, show macro and micro vascular complications associated with hyperglycaemia. Although many trials have demonstrated the efficacy of lifestyle and pharmaceutical interventions in diabetes prevention, no trial has evaluated the extent to which mid- and long-term… Read more about this study
- Who is it for?
- Ages 45 to 74 years
- Conditions the study is for
- PreDiabetes
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,000 participants
- Where
- 1 siteSpain
- Study dates
- 15 Mar 2015to 31 Dec 2019
- 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 45 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Impaired Fasting Glucose (IFG): Fasting Plasma Glucose (FPG) 6.1 to 6.9mmol/l and 2-hour Plasma Glucose (2-h PG): <7.8mmol/L;
- Impaired Glucose Tolerance (IGT): FPG <7.0mmol/L and 2h PG >_7.8 and <11.1 mmol/L -Informed consent given
Who cannot join
- Type 1 diabetes (T1D)
- known or screen-detected Type 2 diabetes (T2D).
- Use of any anti-diabetic drug within the 3 months prior to inclusion.
- Previous cardiovascular event, stroke or revascularization procedure of any arterial territory
- Morbid obesity (BMI>45)
- Current renal replacement therapy.
Show all 30Show fewer
- Renal function impairment: GFR <60 ml/min/1.73m2.
- Previous diagnosis of liver cirrhosis or chronic hepatitis
- Elevation of liver enzymes (AST/AST) >3 times of the upper normal ranges** (6m or BL).
- Previous diagnosis of acute or chronic pancreatitis
- Elevation of pancreatic enzymes (Amylase/Lipase) >3 times of the upper normal ranges (6m or BL).
- Previous diagnosis of Chronic Heart Failure (NYHA class III or higher).
- Organ transplant or waiting for organ transplant.
- Diagnosis of malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years.
- End-stage or metastatic cancer.
- Known or suspected hypersensitivity to trial products or related products.
- Known use of non prescribed narcotics or illicit drugs.
- Simultaneous participation in any other clinical trial of an investigational agent.
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant.
- Cataract that impedes the retinal evaluation of both eyes.
- Ocular surgery planned in the next 6 months
- Concomitant intraocular treatment (retina or choroid).
- Tropicamide allergy
- Participants with screen retinogram not optimal for retinal assessment
- Complete amputation of one/ both hands or one/both feet.
- Dementia, mental disorder or evident cognitive impairment unable to give informed consent.
- Institutionalization (nursing/mental health home, hospital, prison, etc).
- Suspected renal artery stenosis Recent gastrointestinal bleeding (within the last year)
- Any circumstance where ongoing medication might lead to potential adverse drug effect.
- Any other acute condition or exacerbation of chronic condition that in the investigator's opinion would interfere with the trial initiation or visit schedules or procedures.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Centro de Salud Jose Marva
Madrid, 28030
Esther Sanchez, MD, +34629
Ana M Santos
About this study
Official title: Early Prevention of Diabetes Complications in People With Hyperglycaemia in Europe: e-PREDICE Study
Background: A significant proportion of pre-diabetics, show macro and micro vascular complications associated with hyperglycaemia. Although many trials have demonstrated the efficacy of lifestyle and pharmaceutical interventions in diabetes prevention, no trial has evaluated the extent to which mid- and long-term complications can be prevented by early interventions on hyperglycaemia.
Aims: To assess the long-term effects on multiple complications of hyperglycaemia of early intensive management of hyperglycaemia with linagliptin, metformin or their combination added to lifestyle intervention (LSI) (diet and physical activity), compared with LSI alone in adults with non-diabetic intermediate hyperglycaemia (IFG, IGT or both).
Read more
Study Design: Investigator initiated (non-commercial), long-term, multi-centre, randomised, partially double blinded, placebo controlled, phase-IIIb clinical trial with prospective blinded outcome evaluation. Participants will be randomised to four parallel arms: 1) LSI + 2 placebo tablets/day; 2) LSI + 2 Metformin tablets of 850 mg/day; 3) LSI + 1 Linagliptin tablets of 5 mg/day and 1 placebo; 4) LSI + 2 tablets of a fixed-dose combination of Linagliptin 2.5mg and Metformin 850 /day. Active intervention will last for at least 2 years.
Setting and population: Males and Females with pre-diabetes (IFG, IGT or both) aged 45 to 74 years selected from primary care screening programs in 14 clinical centres from 10 countries: Australia, Austria, Bulgaria, Greece, Italy, Kuwait, Poland, Serbia, Spain and Turkey and . (N=1000)
Main Outcomes: The primary endpoint is a combined continous variable: "the microvascular complication índex" (MCI) composed by a linear combination of the Early Treatment Diabetic Retinopathy Study Scale (ETDRS) score (based on retinograms), the level of urinary albumin to creatinine ratio, and a measure of distal small fibre neuropathy (sudomotor test by SUDOSCAN), measured during baseline visit and at 24th and 48th month visits after randomisation. In addition, serological biomarkers of inflammation, vascular damage, non-alcoholic fatty liver disease, insulin secretion, measures of quality of life, sleep quality, neuropsychological evaluation and endothelial function will be also evaluated in a subset of participants.
- Conditions
- PreDiabetes
- Being tested
- Placebo, metformin, linagliptin, linagliptin + metformin
- Keywords
- prediabetes lifestyle drugs microvascular complications
- Medical subject headings
- Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo, metformin, linagliptin, linagliptin + metforminDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | * Placebo
* Lifestyle modification (diet and physical activity recommendations) Receives: Drug: Placebo, metformin, linagliptin, linagliptin + metformin |
| Metformin | Experimental | * Metformin
* Lifestyle modification (diet and physical activity recommendations) Receives: Drug: Placebo, metformin, linagliptin, linagliptin + metformin |
| Linagliptin | Experimental | * Linagliptin
* Lifestyle modification (diet and physical activity recommendations) Receives: Drug: Placebo, metformin, linagliptin, linagliptin + metformin |
| Linagliptin and Metformin | Experimental | * Fixed dose combination of Linagliptin and metformin
* Lifestyle modification (diet and physical activity recommendations) Receives: Drug: Placebo, metformin, linagliptin, linagliptin + metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microvascular Complication Index "MIC" :
linear combination of three continous variables: ETRSD score, UACR and sudomotor index
Measured: 2-year
Diabetic Retinopathy: Scale ETDRS
ETDRS Score
Measured: 2-year
Urine albumin to creatinine ratio (UACR)
Ratio albumin to creatinine in mg/dl
Measured: 2-year
Sudomotor Index
SUDOSCAN sweat function
Measured: 2-year
Secondary outcomes (8)
incidence of diabetes
new cases of Type 2 Diabetes
Measured: 2-year
endothelial dysfunction
ENDOPATH measurement
Measured: 2-year
Insulin sensitivity
Insulin secretion and beta-cell function
Measured: 2-year
Inflammation biomarkers
Measured: 2-years
NAFLD biomarkers
Measured: 2-year
Quality of life
D15 questionnaire.
Measured: 2-year
cognitive function
MMSE questionnaire
Measured: 2-year
depressive symptoms
WHO-MINI questionnaire
Measured: 2-year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2017
- Study start15 Mar 2015
- Primary completion31 Dec 2018 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PreDiabetesStudies 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
- Model description
- Randomized, parallel , single-blind, placebo controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Evidem Consultores SL
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- European Commission, Boehringer Ingelheim, Merck Serono International SA
- Responsible party
- Sponsor
- Investigators
- Rafael Gabriel, MD, PhD, Principal investigator, Evidem Consultores SLJaakko Tuomilehto, MD, PhD, Principal investigator, Evidem Consultores SL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03222765
- Sponsor's protocol ID
- EU-FP7 279074
- Acronym
- ePREDICE
- Status last verified
- Jun 2017
- First submitted
- 20 Jun 2017
- Last updated
- 19 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.
PubMed 38837240Gabriel R, Boukichou Abdelkader N, Acosta T, Gilis-Januszewska A, Gomez-Huelgas R, Makrilakis K, Kamenov Z, Paulweber B, Satman I, Djordjevic P, Alkandari A, Mitrakou A, Lalic N, Colagiuri S, Lindstrom J, Egido J, Natali A, Pastor JC, Teuschl Y, Lind M, Silva L, Lopez-Ridaura R, Tuomilehto J; e-PREDICE Consortium. Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data. PLoS One. 2020 Apr 13;15(4):e0231196. doi: 10.1371/journal.pone.0231196. eCollection 2020.
PubMed 32282852
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Prevention of Diabetes Complications in People With Hyperglycaemia in Europe: e-PREDICE Study
- ClinicalTrials.gov ID
- NCT03222765
- Acronym / sponsor ID
- ePREDICE / EU-FP7 279074
- Conditions
- PreDiabetes
- Keywords
- prediabetes lifestyle drugs microvascular complications
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Evidem Consultores SLIndustry (pharma, biotech, devices)
- Collaborators
- European Commission, Boehringer Ingelheim, Merck Serono International SA
- Study start
- 15 Mar 2015 (actual)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 19 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.
Background: A significant proportion of pre-diabetics, show macro and micro vascular complications associated with hyperglycaemia. Although many trials have demonstrated the efficacy of lifestyle and pharmaceutical interventions in diabetes prevention, no trial has evaluated the extent to which mid- and long-term complications can be prevented by early interventions on hyperglycaemia.
Aims: To assess the long-term effects on multiple complications of hyperglycaemia of early intensive management of hyperglycaemia with linagliptin, metformin or their combination added to lifestyle intervention (LSI) (diet and physical activity), compared with LSI alone in adults with non-diabetic intermediate hyperglycaemia (IFG, IGT or both).
Study Design: Investigator initiated (non-commercial), long-term, multi-centre, randomised, partially double blinded, placebo controlled, phase-IIIb clinical trial with prospective blinded outcome evaluation. Participants will be randomised to four parallel arms: 1) LSI + 2 placebo tablets/day; 2) LSI + 2 Metformin tablets of 850 mg/day; 3) LSI + 1 Linagliptin tablets of 5 mg/day and 1 placebo; 4) LSI + 2 tablets of a fixed-dose combination of Linagliptin 2.5mg and Metformin 850 /day. Active intervention will last for at least 2 years.
Setting and population: Males and Females with pre-diabetes (IFG, IGT or both) aged 45 to 74 years selected from primary care screening programs in 14 clinical centres from 10 countries: Australia, Austria, Bulgaria, Greece, Italy, Kuwait, Poland, Serbia, Spain and Turkey and . (N=1000)
Main Outcomes: The primary endpoint is a combined continous variable: "the microvascular complication índex" (MCI) composed by a linear combination of the Early Treatment Diabetic Retinopathy Study Scale (ETDRS) score (based on retinograms), the level of urinary albumin to creatinine ratio, and a measure of distal small fibre neuropathy (sudomotor test by SUDOSCAN), measured during baseline visit and at 24th and 48th month visits after randomisation. In addition, serological biomarkers of inflammation, vascular damage, non-alcoholic fatty liver disease, insulin secretion, measures of quality of life, sleep quality, neuropsychological evaluation and endothelial function will be also evaluated in a subset of participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized, parallel , single-blind, placebo controlled
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, metformin, linagliptin, linagliptin + metformin* Placebo * Lifestyle modification (diet and physical activity recommendations) |
| Metformin | Experimental | Drug: Placebo, metformin, linagliptin, linagliptin + metformin* Metformin * Lifestyle modification (diet and physical activity recommendations) |
| Linagliptin | Experimental | Drug: Placebo, metformin, linagliptin, linagliptin + metformin* Linagliptin * Lifestyle modification (diet and physical activity recommendations) |
| Linagliptin and Metformin | Experimental | Drug: Placebo, metformin, linagliptin, linagliptin + metformin* Fixed dose combination of Linagliptin and metformin * Lifestyle modification (diet and physical activity recommendations) |
Who may qualify
- Ages
- 45 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Impaired Fasting Glucose (IFG): Fasting Plasma Glucose (FPG) 6.1 to 6.9mmol/l and 2-hour Plasma Glucose (2-h PG): <7.8mmol/L;
- Impaired Glucose Tolerance (IGT): FPG <7.0mmol/L and 2h PG >_7.8 and <11.1 mmol/L -Informed consent given
Key exclusion criteria (30 listed)
- Type 1 diabetes (T1D)
- known or screen-detected Type 2 diabetes (T2D).
- Use of any anti-diabetic drug within the 3 months prior to inclusion.
- Previous cardiovascular event, stroke or revascularization procedure of any arterial territory
- Morbid obesity (BMI>45)
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 |
|---|---|---|
| Placebo, metformin, linagliptin, linagliptin + metformin | Drug | Linagliptin, Linagliptin and Metformin, Metformin, Placebo |
Primary outcome
Microvascular Complication Index "MIC" :
Time frame: 2-year
linear combination of three continous variables: ETRSD score, UACR and sudomotor index
Diabetic Retinopathy: Scale ETDRS
Time frame: 2-year
ETDRS Score
Urine albumin to creatinine ratio (UACR)
Time frame: 2-year
Ratio albumin to creatinine in mg/dl
Sudomotor Index
Time frame: 2-year
SUDOSCAN sweat function
8 secondary outcomes
incidence of diabetes
Time frame: 2-year
endothelial dysfunction
Time frame: 2-year
Insulin sensitivity
Time frame: 2-year
Inflammation biomarkers
Time frame: 2-years
NAFLD biomarkers
Time frame: 2-year
Quality of life
Time frame: 2-year
cognitive function
Time frame: 2-year
depressive symptoms
Time frame: 2-year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2017.
- Derived from this study: PubMed 38837240El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.
- Derived from this study: PubMed 32282852Gabriel R, Boukichou Abdelkader N, Acosta T, Gilis-Januszewska A, Gomez-Huelgas R, Makrilakis K, Kamenov Z, Paulweber B, Satman I, Djordjevic P, Alkandari A, Mitrakou A, Lalic N, Colagiuri S, Lindstrom J, Egido J, Natali A, Pastor JC, Teuschl Y, Lind M, Silva L, Lopez-Ridaura R, Tuomilehto J; e-PREDICE Consortium. Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data. PLoS One. 2020 Apr 13;15(4):e0231196. doi: 10.1371/journal.pone.0231196. eCollection 2020.
- Webpage ePREDICE ProjectLink provided by the sponsor.
- 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.
Rafael Gabriel, MD, PhD principal investigator
Evidem Consultores SL
Jaakko Tuomilehto, MD, PhD principal investigator
Evidem Consultores SL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of PreDiabetes, run by Evidem Consultores SL at 1 site in Spain.
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 2 inclusion and 30 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: status not confirmed, as of the sponsor's last update on 19 Jul 2017. 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 Spain. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nisa Boukichou, Ms (+34914025066, nisa@ceiis.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Microvascular Complication Index "MIC" : (time frame: 2-year). The study lists 4 primary outcomes in all. 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 NCT03222765, which also lists 2 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 19 Jul 2017.