ObesityPhase 2GPD-01-01NCT02777489
Influence of Carboxypeptidase D (CPD) Gene on Body Weight and Fat Mass Reduction by Perindopril in Obese Subjects
A Phase 2 study testing Perindopril in people with Obesity, run by Gene PreDiT at 13 sites in Portugal.
Trial summary
The primary objective of this study is to evaluate the Carboxipeptidase D (CPD) genotyping as a predictive biomarker of body weight and/or fat mass reduction in obese patients treated with perindopril. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity
- What is being tested?
- Perindopril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 13 sitesPortugal
- Study dates
- 18 Feb 2016to 27 Apr 2017
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent;
- Man or woman with 18 years or more;
- Body Mass Index (BMI) between 30.0 to 40.0 kg/m2;
- Willingness and ability to comply with the study requirements;
- Ability to understand and sign informed consent;
- If woman of childbearing potential, she agrees to adopt effective contraceptive methods.
Who cannot join
- Pregnant or breastfeeding women;
- History of obesity with a known cause (e.g., hypothyroidism, Cushing's disease);
- Under treatment with perindopril or other angiotensin converting enzyme (ACE) inhibitor, or with an angiotensin receptor blocker (ARB) or a renin inhibitor;
- Hypertension diagnosed at screening;
- Significant variation in weight (more 10%) in the past 3 months before screening visit;
- History of anorexia nervosa, bulimia, or binge-eating disorder;
Show all 23Show fewer
- Systolic blood pressure <110 mmHg;
- History of hypersensitivity to perindopril, or related compounds, or to any of the inactive ingredients;
- History of angioedema associated with previous ACE inhibitor therapy;
- History of idiopathic or hereditary angioedema;
- Treatment with concomitant medication affecting weight loss (e.g. metformin) starting within the 3 months prior to screening;
- Treatment with concomitant medication that might interfere with the absorption, distribution, metabolism or elimination of perindopril, or, is likely to compromise the safety of subject (e.g. diuretics in patients with salt and/or volume depletion, insulin or oral antidiabetics in patients prone to develop hypoglycemic episodes, lithium, vasodilators in patients prone to develop hypotension, tricyclic antidepressants, antipsychotics, anesthetics, gold, potassium supplements or potassium-containing salt substitutes);
- Treatment with any investigational drug or device within 1 month before the start of the run-in period;
- Moderate to severe hepatic impairment (Child-Pugh score ≥ 7) or moderate to severe renal impairment (glomerular filtration rate (GFR) ≤ 59 ml/min);
- Unstable coronary artery disease;
- Aortic and mitral valve stenosis / hypertrophic cardiomyopathy
- Hemodialysis patients;
- Kidney transplantation;
- Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis;
- Neutropenia/agranulocytosis/thrombocytopenia/anemia;
- Patients undergoing major surgery or during anesthesia with agents that produce hypotension;
- Hyperkalemia;
- Any other condition or therapy that the study physician considers to make the subject unsuitable for this study
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Portugal13 sites
Unidade de Saúde Familiar Escariz
Arouca, 4540-297
Centro Hospitalar do Baixo Vouga (CHBV), EPE
Aveiro, 3814-501
Unidade de Saúde Familiar Canelas
Canelas, 4410 - 273
Centro Hospitalar Cova da Beira (CHCB), EPE
Covilha, 6200-251
Unidade de Saúde Familiar Lethes
Ponte de Lima, 4990-145
Centro Hospitalar de São João (CHSJ), E.P.E
Porto, 4200-319
Unidade de Saúde Familiar Arca d'Água
Porto, 4200-510
Unidade de Cuidados de Saúde Personalizados Carvalhido
Porto, 4250-113
Unidade Local de Saúde do Alto Minho (ULSAM), E.P.E.
Viana do Castelo, 4901 - 858
Unidade de Saúde Familiar Nova Salus
Vila Nova de Gaia, 4400-043
Unidade de Saúde Familiar Santo André de Canidelo
Vila Nova de Gaia, 4400-230
Centro Hospitalar V.N.Gaia/Espinho (CHVNG/E)- Endocrinology
Vila Nova de Gaia, 4434-502
Centro Hospitalar Vila Nova de Gaia/Espinho (CHVNG/E)
Vila Nova de Gaia, 4434-502
About this study
Official title: Influence of Single Nucleotide Polymorphisms of Carboxypeptidase D (CPD) Gene on Body Weight and Fat Mass Reduction by Perindopril in Obese Subjects: A Phase II, Multicenter, Double-blind Study
The primary objective of this study is to evaluate the Carboxipeptidase D (CPD) genotyping as a predictive biomarker of body weight and/or fat mass reduction in obese patients treated with perindopril.
There is nonclinical and clinical evidence that a subgroup of human subjects may present a decrease in body weight and/or fat mass following treatment with perindopril. Although the individual characteristics that determine such effect are still unknown, Gene PreDiT SA (Biocant Park, Cantanhede, Portugal) discovered that certain genetic characteristics (e.g., single nucleotide polymorphisms (SNPs) of CPD gene) may play a role and potentially could serve as a potential predictive biomarker of response to perindopril.
Read more
These promising results, along with the fact that perindopril is a medicine already in use in clinical practice, led Gene PreDiT SA to decide to proceed with the development of a theranostic approach for the treatment of obesity. Such theranostic approach consists on the use of CPD genotyping to identify obese subjects that could present improved body weight and fat mass reduction following treatment with perindopril.
The current clinical trial aims to prove the concept and provide data to design further confirmatory studies. Additionally this study will evaluate the association between CPD SNPs genotypes and response to perindopril; the effect of perindopril in waist circumference, waist/hip ratio, and BMI and the tolerability and safety of perindopril in the study population.
Read the detailed description
The study consists of 2 periods and 4 visits (V): a run-in period of at least 4 weeks (V1 to V2) and a 12-week perindopril treatment period (V2 to V4).
After written informed consent, patients will undergo screening evaluations (V1). Patients who meet the selection criteria will enter a run-in period of 4 weeks where they will be given dietary and exercise counseling as standardized non-drug therapy. After the run-in period (V2), patients will start the pharmacological therapy period where they will receive perindopril 8 mg, once daily, for 12 weeks, concomitantly with the previously established standardized non-drug therapy.
During the 12-week pharmacological treatment, patients will attend an intermediate study visit (V3) at approximately 6 weeks and a final visit (V4) for efficacy and safety assessments.
Body weight, body mass index (BMI), waist and hip circumference, and body fat mass estimation will be assessed at every study visit.
A total of 160 subjects will be enrolled, to have approximately 120 subjects evaluable.
After V2, patients will be administered perindopril 8 mg, once daily, for 12 weeks, concomitantly with the previously established standardized non-pharmacological therapy.
Blood sampling for clinical safety laboratory assessments (hematology and plasma biochemistry) will be collected at the screening, at the end of the run-in period, at the intermediate treatment visit, and at the end of the perindopril treatment period.
At the screening, blood will also be collected for CPD genotyping, but the results will remain blinded until database closure.
Safety will be evaluated through the assessment of treatment-emergent adverse events, vital signs and clinical laboratory tests. Adverse events will be monitored throughout the study. Vital signs will be recorded at each scheduled visit. Clinical safety laboratory parameters will be collected at screening, end of the run-in period, at the intermediate treatment visit, and at the end of the treatment period.
Abnormalities in vital signs and laboratory parameters will be assessed by the clinical investigator in terms of clinical relevance. Clinically significant abnormalities in clinical laboratory and vital signs will be reported as adverse events.
Associations between CPD SNPs genotypes and patient response will be assessed through the appropriate statistical methods. The primary efficacy analysis will compare the response rate in the group of subjects with the SNPs of interest and the group of the remaining subjects. A logistic regression model will be used to assess the group differences. Weight and fat mass at the start of the perindopril treatment period and gender will be used as covariates. Other covariates will be investigated for exploratory purposes, but will not be included in the model where main treatment effects are tested and compared. All the secondary efficacy endpoints will be assessed using analysis of covariance (ANCOVA). In general, the principles applied for the primary efficacy analysis will be replicated for the secondary efficacy analysis.
Adverse events will be tabulated and summarized according to system organ class (SOC) and preferred term (PT).
- Conditions
- Obesity
- Being tested
- Perindopril
- Keywords
- obesity, perindopril, carboxypeptidase D, genotyping, theranostic
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerindoprilDrug
Perindopril Bluepharma 8 mg tablets, daily, during approximately 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Perindopril Bluepharma 8 mg | Experimental | Each participant will have an at least 4-week run-in period, followed by a 6 weeks treatment period with Perindopril 8 mg. Receives: Drug: Perindopril |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate, defined as the proportion of patients who will lose at least 3% of body weight and/or at least 3% of fat mass from end of the run-in period to the end of the perindopril treatment period.
Measured: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
Secondary outcomes (7)
End vs start of treatment relative change in body weight.
Measured: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
End vs start of treatment relative change in fat mass.
Measured: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
End vs start of treatment relative change in waist circumference.
Measured: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
End vs start of treatment relative change in hip circumference.
Measured: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
End vs start of treatment relative change in fasting lipid profile.
Measured: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
Frequency and type of adverse events.
Measured: From V1 until the end of the perindopril treatment period, , up to 16 weeks
Response rate, defined as the proportion of patients who will lose at least 5% of body weight and/or at least 5% of fat mass from end of the run-in period to the end of the perindopril treatment period.
Measured: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2016 (estimated)
- Study start18 Feb 2016
- Primary completion18 Jan 2017
- Study completion27 Apr 2017
Why it stopped: Unproven hypothesis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gene PreDiT
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Blueclinical, Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02777489
- Sponsor's protocol ID
- GPD-01-01
- Acronym
- GPD-01-01
- Status last verified
- Aug 2017
- First submitted
- 7 Mar 2016
- Last updated
- 3 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Single Nucleotide Polymorphisms of Carboxypeptidase D (CPD) Gene on Body Weight and Fat Mass Reduction by Perindopril in Obese Subjects: A Phase II, Multicenter, Double-blind Study
- ClinicalTrials.gov ID
- NCT02777489
- Acronym / sponsor ID
- GPD-01-01 / GPD-01-01
- Conditions
- Obesity
- Keywords
- obesity, perindopril, carboxypeptidase D, genotyping, theranostic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unproven hypothesis
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Gene PreDiTIndustry (pharma, biotech, devices)
- Collaborators
- Blueclinical, Ltd.
- Study start
- 18 Feb 2016
- Primary completion
- 18 Jan 2017 (actual)
- Study completion
- 27 Apr 2017 (actual)
- First posted
- 19 May 2016 (estimated)
- 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.
The primary objective of this study is to evaluate the Carboxipeptidase D (CPD) genotyping as a predictive biomarker of body weight and/or fat mass reduction in obese patients treated with perindopril.
There is nonclinical and clinical evidence that a subgroup of human subjects may present a decrease in body weight and/or fat mass following treatment with perindopril. Although the individual characteristics that determine such effect are still unknown, Gene PreDiT SA (Biocant Park, Cantanhede, Portugal) discovered that certain genetic characteristics (e.g., single nucleotide polymorphisms (SNPs) of CPD gene) may play a role and potentially could serve as a potential predictive biomarker of response to perindopril.
These promising results, along with the fact that perindopril is a medicine already in use in clinical practice, led Gene PreDiT SA to decide to proceed with the development of a theranostic approach for the treatment of obesity. Such theranostic approach consists on the use of CPD genotyping to identify obese subjects that could present improved body weight and fat mass reduction following treatment with perindopril.
The current clinical trial aims to prove the concept and provide data to design further confirmatory studies. Additionally this study will evaluate the association between CPD SNPs genotypes and response to perindopril; the effect of perindopril in waist circumference, waist/hip ratio, and BMI and the tolerability and safety of perindopril in the study population.
Detailed description
The study consists of 2 periods and 4 visits (V): a run-in period of at least 4 weeks (V1 to V2) and a 12-week perindopril treatment period (V2 to V4).
After written informed consent, patients will undergo screening evaluations (V1). Patients who meet the selection criteria will enter a run-in period of 4 weeks where they will be given dietary and exercise counseling as standardized non-drug therapy. After the run-in period (V2), patients will start the pharmacological therapy period where they will receive perindopril 8 mg, once daily, for 12 weeks, concomitantly with the previously established standardized non-drug therapy.
During the 12-week pharmacological treatment, patients will attend an intermediate study visit (V3) at approximately 6 weeks and a final visit (V4) for efficacy and safety assessments.
Body weight, body mass index (BMI), waist and hip circumference, and body fat mass estimation will be assessed at every study visit.
A total of 160 subjects will be enrolled, to have approximately 120 subjects evaluable.
After V2, patients will be administered perindopril 8 mg, once daily, for 12 weeks, concomitantly with the previously established standardized non-pharmacological therapy.
Blood sampling for clinical safety laboratory assessments (hematology and plasma biochemistry) will be collected at the screening, at the end of the run-in period, at the intermediate treatment visit, and at the end of the perindopril treatment period.
At the screening, blood will also be collected for CPD genotyping, but the results will remain blinded until database closure.
Safety will be evaluated through the assessment of treatment-emergent adverse events, vital signs and clinical laboratory tests. Adverse events will be monitored throughout the study. Vital signs will be recorded at each scheduled visit. Clinical safety laboratory parameters will be collected at screening, end of the run-in period, at the intermediate treatment visit, and at the end of the treatment period.
Abnormalities in vital signs and laboratory parameters will be assessed by the clinical investigator in terms of clinical relevance. Clinically significant abnormalities in clinical laboratory and vital signs will be reported as adverse events.
Associations between CPD SNPs genotypes and patient response will be assessed through the appropriate statistical methods. The primary efficacy analysis will compare the response rate in the group of subjects with the SNPs of interest and the group of the remaining subjects. A logistic regression model will be used to assess the group differences. Weight and fat mass at the start of the perindopril treatment period and gender will be used as covariates. Other covariates will be investigated for exploratory purposes, but will not be included in the model where main treatment effects are tested and compared. All the secondary efficacy endpoints will be assessed using analysis of covariance (ANCOVA). In general, the principles applied for the primary efficacy analysis will be replicated for the secondary efficacy analysis.
Adverse events will be tabulated and summarized according to system organ class (SOC) and preferred term (PT).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Perindopril Bluepharma 8 mg | Experimental | Drug: PerindoprilEach participant will have an at least 4-week run-in period, followed by a 6 weeks treatment period with Perindopril 8 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent;
- Man or woman with 18 years or more;
- Body Mass Index (BMI) between 30.0 to 40.0 kg/m2;
- Willingness and ability to comply with the study requirements;
- Ability to understand and sign informed consent;
Key exclusion criteria (23 listed)
- Pregnant or breastfeeding women;
- History of obesity with a known cause (e.g., hypothyroidism, Cushing's disease);
- Under treatment with perindopril or other angiotensin converting enzyme (ACE) inhibitor, or with an angiotensin receptor blocker (ARB) or a renin inhibitor;
- Hypertension diagnosed at screening;
- Significant variation in weight (more 10%) in the past 3 months before screening visit;
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 |
|---|---|---|
| PerindoprilPerindopril Bluepharma 8 mg tablets, daily, during approximately 12 weeks | Drug | Perindopril Bluepharma 8 mg |
Primary outcome
Response rate, defined as the proportion of patients who will lose at least 3% of body weight and/or at least 3% of fat mass from end of the run-in period to the end of the perindopril treatment period.
Time frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
7 secondary outcomes
End vs start of treatment relative change in body weight.
Time frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
End vs start of treatment relative change in fat mass.
Time frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
End vs start of treatment relative change in waist circumference.
Time frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
End vs start of treatment relative change in hip circumference.
Time frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
End vs start of treatment relative change in fasting lipid profile.
Time frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
Frequency and type of adverse events.
Time frame: From V1 until the end of the perindopril treatment period, , up to 16 weeks
Response rate, defined as the proportion of patients who will lose at least 5% of body weight and/or at least 5% of fat mass from end of the run-in period to the end of the perindopril treatment period.
Time frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks
Results and safety
The study was stopped early (reason given: Unproven hypothesis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2017.
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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.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Perindopril in people with Obesity, run by Gene PreDiT at 13 sites in Portugal.
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 23 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: stopped early, as of the sponsor's last update on 3 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Portugal. 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 was stopped early (reason given: Unproven hypothesis). Results are not available in the source record.
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?
Response rate, defined as the proportion of patients who will lose at least 3% of body weight and/or at least 3% of fat mass from end of the run-in period to the end of the perindopril treatment period. (time frame: From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks). 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 3 Aug 2017.