Influence of Carboxypeptidase D (CPD) Gene on Body Weight and Fat Mass Reduction by Perindopril in Obese Subjects

NCT02777489 | Terminated Phase 2

• 1 other identifier: GPD-01-01
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 13

Brief 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. 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.

Conditions

Obesity

Keywords

obesity; perindopril; carboxypeptidase D; genotyping; theranostic

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  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.

  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.

  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.

  From end of the run-in period to the end of the perindopril treatment period, up to 12 weeks

Study Arms (1)

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.

Drug: Perindopril

Interventions

Perindopril DRUG

Perindopril Bluepharma 8 mg tablets, daily, during approximately 12 weeks

Perindopril Bluepharma 8 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Gene PreDiT: lead
• Blueclinical, Ltd.: collaborator

Study Sites (13)

Unidade de Saúde Familiar Escariz

Arouca, 4540-297, Portugal

Location

Centro Hospitalar do Baixo Vouga (CHBV), EPE

Aveiro, 3814-501, Portugal

Location

Unidade de Saúde Familiar Canelas

Canelas, 4410 - 273, Portugal

Location

Centro Hospitalar Cova da Beira (CHCB), EPE

Covilha, 6200-251, Portugal

Location

Unidade de Saúde Familiar Lethes

Ponte de Lima, 4990-145, Portugal

Location

Centro Hospitalar de São João (CHSJ), E.P.E

Porto, 4200-319, Portugal

Location

Unidade de Saúde Familiar Arca d'Água

Porto, 4200-510, Portugal

Location

Unidade de Cuidados de Saúde Personalizados Carvalhido

Porto, 4250-113, Portugal

Location

Unidade Local de Saúde do Alto Minho (ULSAM), E.P.E.

Viana do Castelo, 4901 - 858, Portugal

Location

Unidade de Saúde Familiar Nova Salus

Vila Nova de Gaia, 4400-043, Portugal

Location

Unidade de Saúde Familiar Santo André de Canidelo

Vila Nova de Gaia, 4400-230, Portugal

Location

Centro Hospitalar V.N.Gaia/Espinho (CHVNG/E)- Endocrinology

Vila Nova de Gaia, 4434-502, Portugal

Location

Centro Hospitalar Vila Nova de Gaia/Espinho (CHVNG/E)

Vila Nova de Gaia, 4434-502, Portugal

Location

MeSH Terms

Conditions

Obesity

Interventions

Perindopril

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2016
• First Posted: May 19, 2016
• Study Start: February 18, 2016
• Primary Completion: January 18, 2017
• Study Completion: April 27, 2017
• Last Updated: August 3, 2017

Record last verified: 2017-08

Locations

PT (13)