Diabetes, Hypertension
Conditions
Keywords
diabetes, blood pressure, pioglitazone, sodium, insulin resistance, renal function, sodium, pioglitazone
Brief summary
This study examines the effects of pioglitazone on renal sodium handling in subjects prone to insulin resistance, i.e. diabetic and/or hypertensive subjects.
Detailed description
Aim: Glitazones are powerful insulin sensitizers prescribed for the treatment of type 2 diabetes. Their use is however associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in subjects prone to insulin resistance, i.e. diabetic and/or hypertensive subjects. Methods: In this double-blind, randomized, placebo-controlled, four-way, cross-over study, we examined the effects of pioglitazone (45mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, 8 with type 2 diabetic and 8 with hypertension.
Interventions
DRUGPioglitazone
placebo-controlled, randomized, cross-over study was to explore the effects of pioglitazone (45 mg q.d. for 6 weeks) on the renal, hormonal and blood pressure responses to changes in sodium intake in a population prone to insulin resistance
DRUGMetformin
placebo-controlled, randomized, cross-over study was to explore the effects of pioglitazone (45 mg q.d. for 6 weeks) on the renal, hormonal and blood pressure responses to changes in sodium intake in a population prone to insulin resistance
Sponsors
University of Lausanne Hospitals
University Hospital, Geneva
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Type II Diabetes * Hypertension
Exclusion criteria
* Cardiac or renal diseases * Anaemia * Drugs like aspirin, non steroidal anti-inflammatory drugs and hormonal replacement therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Pioglitazone on Renal Hemodynamics | 2008 | At the end of each treatment diet phase, renal clearances were performed for the determination of GFR and RBF |
| Effects of Pioglitazone on Sodium and Lithium Clearances | 2007 | At the end of each treatment and diet phase, 24 urine collections were collected for the determination of sodium and lithium clearances |
| Effects of Pioglitazone on 24h Blood Pressure Control | march 2009 | 24 hour blood pressure measurements were performed after each treatment/diet phase |
Secondary
| Measure | Time frame |
|---|---|
| Effects of Pioglitazone on Salt Sensitivity | 2009 |
Countries
Switzerland
Participant flow
Recruitment details
Sixteen subjects were examined, 8 with a diagnosis of type 2 diabetes (DM2) and 8 with a diagnosis of systemic hypertension (HTN). The participants were recruited by hospital placards detailing the study, and through ambulatory care centers in Lausanne and Geneva.
Pre-assignment details
Each subject was randomised to receive either pioglitazone or placebo for 6 weeks, with a 2 week wash-out period between the two treatment phases. Randomisation of the sequences of placebo and active treatment periods were performed by a doctor having no contact with participants and clinicians.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Low Salt/High Salt a low salt and a high salt diet were given consequently and randomly during a week at the end of the pioglitazone phase | 8 |
| Placebo Low Salt/High Salt a low salt and a high salt diet were given consequently and randomly during a week at the end of the placebo phase | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo Low Salt/High Salt | Pioglitazone Low Salt/High Salt | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 16 Participants |
| Age Continuous | 52.5 years STANDARD_DEVIATION 2.8 | 52.5 years STANDARD_DEVIATION 2.8 | 52.5 years STANDARD_DEVIATION 2.8 |
| Region of Enrollment Switzerland | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Effects of Pioglitazone on 24h Blood Pressure Control
24 hour blood pressure measurements were performed after each treatment/diet phase
Time frame: march 2009
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Low Salt/High Salt | Effects of Pioglitazone on 24h Blood Pressure Control | 128 mmHg | Standard Error 5 |
| Placebo Low Salt/High Salt | Effects of Pioglitazone on 24h Blood Pressure Control | 129 mmHg | Standard Error 5 |
Primary
Effects of Pioglitazone on Renal Hemodynamics
At the end of each treatment diet phase, renal clearances were performed for the determination of GFR and RBF
Time frame: 2008
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Low Salt/High Salt | Effects of Pioglitazone on Renal Hemodynamics | 68.0 ml/min/1.73m2 | Standard Error 4.4 |
| Placebo Low Salt/High Salt | Effects of Pioglitazone on Renal Hemodynamics | 62.4 ml/min/1.73m2 | Standard Error 5 |
Primary
Effects of Pioglitazone on Sodium and Lithium Clearances
At the end of each treatment and diet phase, 24 urine collections were collected for the determination of sodium and lithium clearances
Time frame: 2007
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone Low Salt/High Salt | Effects of Pioglitazone on Sodium and Lithium Clearances | 1.05 ml/min | Standard Error 0.1 |
| Placebo Low Salt/High Salt | Effects of Pioglitazone on Sodium and Lithium Clearances | 1.18 ml/min | Standard Error 0.13 |
Secondary
Effects of Pioglitazone on Salt Sensitivity
Time frame: 2009