Renal and Hormonal Effects of Pioglitazone

• Sponsor: University Hospital, Geneva (Other)
• Overall Status: Completed
• CT.gov ID: NCT01090752
• Collaborator: University of Lausanne Hospitals (Other)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Hypertension	Drug: Pioglitazone; Drug: Metformin	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of the PPAR-gamma Agonist Pioglitazone on Renal and Hormonal Responses to Salt in Diabetic and Hypertensive Subjects
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Pioglitazone placebo-controlled, randomized, cross-over study	Drug: Pioglitazone; 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; Other Names: Actos ; Drug: Metformin; 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; Other Names: Glucophage Glumetza Fortamet Riomet
Placebo Comparator: Metformine 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	Drug: Metformin; 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; Other Names: Glucophage Glumetza Fortamet Riomet

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

3. Effects of Pioglitazone on 24h Blood Pressure Control [march 2009]

   24 hour blood pressure measurements were performed after each treatment/diet phase

Secondary Outcome Measures

1. Effects of Pioglitazone on Salt Sensitivity [2009]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pechère-Bertschi Antoinette	Geneva		Switzerland	1211

Sponsors and Collaborators

• University Hospital, Geneva
• University of Lausanne Hospitals

Investigators

• Study Director: Antoinette Pechere-Bertschi, MD, University Hospital, Geneva

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01090752
• Other Study ID Numbers: FDAAA
• First Posted: Mar 22, 2010
• Last Update Posted: Apr 8, 2010
• Last Verified: Jan 1, 2009

• Keywords provided by , ,: diabetes; blood pressure; pioglitazone; sodium; insulin resistance, renal function, sodium, pioglitazone
• Additional relevant MeSH terms: Hypertension; Metformin; Pioglitazone

Study Results

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 Detail	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.

Arm/Group Title	Pioglitazone Low Salt/High Salt	Placebo Low Salt/High Salt
Arm/Group Description	a low salt and a high salt diet were given consequently and randomly during a week at the end of the pioglitazone phase	a low salt and a high salt diet were given consequently and randomly during a week at the end of the placebo phase
Period Title: Overall Study
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pioglitazone Low Salt/High Salt	Placebo Low Salt/High Salt	Total
Arm/Group Description	a low salt and a high salt diet were given consequently and randomly during a week at the end of the pioglitazone phase	a low salt and a high salt diet were given consequently and randomly during a week at the end of the placebo phase	Total of all reporting groups
Overall Participants	8	8	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	16 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.5 (2.8)	52.5 (2.8)	52.5 (2.8)
Sex: Female, Male (Count of Participants)
Female	4 50%	4 50%	8 50%
Male	4 50%	4 50%	8 50%
Region of Enrollment (participants) [Number]
Switzerland	8 100%	8 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Effects of Pioglitazone on Renal Hemodynamics
Description	At the end of each treatment diet phase, renal clearances were performed for the determination of GFR and RBF
Time Frame	2008

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone Low Salt/High Salt	Placebo Low Salt/High Salt
Arm/Group Description	a low salt and a high salt diet were given consequently and randomly during a week at the end of the pioglitazone phase	a low salt and a high salt diet were given consequently and randomly during a week at the end of the placebo phase
Measure Participants	16	16
Mean (Standard Error) [ml/min/1.73m2]	68.0 (4.4)	62.4 (5.0)

2. Primary Outcome

Title	Effects of Pioglitazone on Sodium and Lithium Clearances
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone Low Salt/High Salt	Placebo Low Salt/High Salt
Arm/Group Description	a low salt and a high salt diet were given consequently and randomly during a week at the end of the pioglitazone phase	a low salt and a high salt diet were given consequently and randomly during a week at the end of the placebo phase
Measure Participants	16	16
Mean (Standard Error) [ml/min]	1.05 (0.10)	1.18 (0.13)

3. Primary Outcome

Title	Effects of Pioglitazone on 24h Blood Pressure Control
Description	24 hour blood pressure measurements were performed after each treatment/diet phase
Time Frame	march 2009

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pioglitazone Low Salt/High Salt	Placebo Low Salt/High Salt
Arm/Group Description	a low salt and a high salt diet were given consequently and randomly during a week at the end of the pioglitazone phase	a low salt and a high salt diet were given consequently and randomly during a week at the end of the placebo phase
Measure Participants	16	16
Mean (Standard Error) [mmHg]	128 (5)	129 (5)

4. Secondary Outcome

Title	Effects of Pioglitazone on Salt Sensitivity
Time Frame	2009

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Pioglitazone Low Salt/High Salt		Placebo Low Salt/High Salt
Arm/Group Description	a low salt and a high salt diet were given consequently and randomly during a week at the end of the pioglitazone phase		a low salt and a high salt diet were given consequently and randomly during a week at the end of the placebo phase
All Cause Mortality
	Pioglitazone Low Salt/High Salt		Placebo Low Salt/High Salt
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pioglitazone Low Salt/High Salt		Placebo Low Salt/High Salt
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Pioglitazone Low Salt/High Salt		Placebo Low Salt/High Salt
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

The sample size may seem small but the cross over design of the study increased the statistical power. Each of 16 individuals was examined 4 times after the 4 different phases (pioglitazone-low salt, and high salt, placebo low salt and high salt).

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.