Impaired Glucose TolerancePhase 3NCT00220961
Actos Now for Prevention of Diabetes (ACT NOW)
A Phase 3 study testing Pioglitazone in people with Impaired Glucose Tolerance and Type 2 Diabetes, run by The University of Texas Health Science Center at San Antonio at 8 sites in United States.
Trial summary
The purpose of this study is to examine whether pioglitazone versus placebo can reduce the conversion rate of impaired glucose tolerance (IGT) to type 2 diabetes mellitus Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Impaired Glucose Tolerance, Type 2 Diabetes
- What is being tested?
- Pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 602 participants
- Where
- 8 sitesUnited States
- Study dates
- Jan 2004to Apr 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Men and women
- All ethnic groups
- 18 years of age and older
- Impaired glucose tolerance by glucose tolerance test (fasting glucose 95-125 mg/dl and 2 hr glucose of 140-199 mg/dl)
- At least one of the following:
- One or more components of the insulin resistance syndrome (HDL < 40 mg/dl in females and <35 mg/dl in males, fasting triglycerides > 150 mg/dl, blood pressure > 135/85 mmHg, BMI > 24 kg/m2, waist circumference > 102 cm in men and > 88 cm in women)
Show all 10Show fewer
- One or more first degree relatives with type 2 diabetes
- History of gestational diabetes
- Polycystic ovarian disease
- Minority ethnic background (Mexican American, African American, Asian and Pacific Islanders, Native American)
Who cannot join
- Type 2 diabetes
- Previously treated with thiazolidinediones (ever) or metformin (within one year)
- Previously treated with a sulfonylurea, a meglitinide, an alpha glucosidase inhibitor for more than a week within last year or within the 3 months prior to randomization
- Previously treated with insulin (other than during pregnancy) for more than one week within the last year or within the 3 months prior to randomization
- Cardiovascular disease
- Hospitalization for treatment of heart disease or stroke in past 6 months
Show all 31Show fewer
- New York Heart Association Functional Class > 2
- Left bundle branch block or third degree AV block
- Aortic stenosis
- SBP > 180 mmHg or DBP > 105 mmHg
- Renal disease
- Anemia
- Hepatitis
- GI diseases (pancreatitis, inflammatory bowel disease)
- Recent or significant abdominal surgery
- Advanced pulmonary disease
- Chronic infections
- Weight loss > 10% in past 6 months
- Pregnancy and childbearing
- Major psychiatric disorders
- Excessive alcohol intake
- Thiazide use > 25 mg per day
- Non-selective beta blockers
- Niacin
- Systemic glucocorticoids
- Weight loss or weight gain medication
- Thyroid disease-suboptimally treated
- Active endocrine diseases (Cushing's, acromegaly)
- Plasma triglycerides over 400 mg/dl (despite treatment)
- History bladder cancer
- Hematuria
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Pennington Biomedical Research Center
Baton Rouge, Louisiana, 70808
SUNY Health Science Center
Brooklyn, New York, 11203
USC-Keck School of Medicine
Los Angeles, California, 90033
University of Tennessee
Memphis, Tennessee, 38163
Carl T. Hayden VA Medical Center
Phoenix, Arizona, 85012
Texas Diabetes Institute
San Antonio, Texas, 78207
University of California San Diego-San Diego VA Medical Center
San Diego, California, 92161
Georgetown University
Washington D.C., District of Columbia, 20007
About this study
The purpose of this study is to examine whether pioglitazone versus placebo can reduce the conversion rate of impaired glucose tolerance (IGT) to type 2 diabetes mellitus
Read the detailed description
IGT is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, the hyperglycemia-related complications of this devastating disease can be prevented. Subjects with IGT will be identified with an oral glucose tolerance test (OGTT). Eligible subjects also will have a measurement of first phase insulin secretion and insulin sensitivity using the frequently sampled intravenous glucose tolerance test (FSIVGTT) and carotid intimal media thickness using carotid ultrasound. Following these measurements subjects will be randomized to receive pioglitazone or placebo and they will return every 3 months for determination of fasting plasma glucose (FPG) concentration and interim medical history. Recruitment will take place over 15 months. From the time that the recruitment period ends, subjects will be followed for a total of 24 months on pioglitazone or placebo. The OGTT will be repeated at 15,27, and 39 months, or if the FPG is ≥ 126 mg/dl on the 3-month follow up visits. If the diagnosis of diabetes is established before month 39 or at month 39, the FSIVGTT and carotid ultrasound will be repeated. At 39 months, subjects will be washed out of pioglitazone or placebo and the OGTT, FSIVGTT, and carotid ultrasound will be repeated at month 45.
- Conditions
- Impaired Glucose Tolerance, Type 2 Diabetes
- Being tested
- Pioglitazone, Placebo
- Keywords
- Impaired Glucose Tolerance, Type 2 Diabetes, Prevention, Pioglitazone
- Medical subject headings
- Glucose Intolerance, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
Pioglitazone tablets - 45 mg/day
PlaceboDrug
Placebo tablets similar to pioglitazone tablets - 1 tablet/day
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo tablet similar to pioglitazone tablet Receives: Drug: Placebo |
| Pioglitazone | Active comparator | Pioglitazone tablet similar to placebo tablet Receives: Drug: Pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevention of Type 2 Diabetes
Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization
Measured: 2.4 years
Secondary outcomes (4)
Change From Baseline in Fasting Plasma Glucose of 2.4 Years
Fasting Plasma Glucose
Measured: Baseline versus 2.4 years
Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test
Insulin secretion
Measured: Baseline versus 2.4 years
Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values)
Insulin sensitivity The Matsuda index was calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin), with higher numbers indicating better the insulin sensitivity.
Measured: Baseline versus 2.4 years
Change in Atherosclerosis
carotid intima thickness
Measured: Baseline versus 2.4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startJan 2004
- Primary completionApr 2010
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Impaired Glucose ToleranceStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 602 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- University of Texas, Takeda Pharmaceuticals North America, Inc.
- Responsible party
- Principal investigator, Ralph DeFronzo, MD, The University of Texas Health Science Center at San Antonio
- Investigators
- Ralph A. DeFronzo, M.D., Principal investigator, Texas Diabetes Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00220961
- Sponsor's protocol ID
- 02-062A
- Status last verified
- Jun 2016
- First submitted
- 14 Sep 2005
- Last updated
- 11 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Ipsen EO, Madsen KS, Chi Y, Pedersen-Bjergaard U, Richter B, Metzendorf MI, Hemmingsen B. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 19;11(11):CD013516. doi: 10.1002/14651858.CD013516.pub2.
PubMed 33210751Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Musi N, Reaven PD, DeFronzo RA. Diabetes Incidence and Glucose Tolerance after Termination of Pioglitazone Therapy: Results from ACT NOW. J Clin Endocrinol Metab. 2016 May;101(5):2056-62. doi: 10.1210/jc.2015-4202. Epub 2016 Mar 16.
PubMed 26982008Tripathy D, Cobb JE, Gall W, Adam KP, George T, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Reaven PD, Musi N, Ferrannini E, DeFronzo RA. A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study. J Clin Endocrinol Metab. 2015 May;100(5):1855-62. doi: 10.1210/jc.2014-3824. Epub 2015 Jan 20.
PubMed 25603459Tripathy D, Clement SC, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Gastaldelli A, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Musi N, Reaven PD, DeFronzo RA. Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW. Diabetes Care. 2014 Jun;37(6):1706-11. doi: 10.2337/dc13-1745. Epub 2014 Apr 4.
PubMed 24705615Saremi A, Schwenke DC, Buchanan TA, Hodis HN, Mack WJ, Banerji M, Bray GA, Clement SC, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Musi N, Tripathy D, DeFronzo RA, Reaven PD. Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):393-9. doi: 10.1161/ATVBAHA.112.300346. Epub 2012 Nov 21.
PubMed 23175674DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Hodis HN, Kitabchi AE, Mack WJ, Mudaliar S, Ratner RE, Williams K, Stentz FB, Musi N, Reaven PD; ACT NOW Study. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011 Mar 24;364(12):1104-15. doi: 10.1056/NEJMoa1010949.
PubMed 21428766Defronzo RA, Banerji M, Bray GA, Buchanan TA, Clement S, Henry RR, Kitabchi AE, Mudaliar S, Musi N, Ratner R, Reaven PD, Schwenke D, Stentz FB, Tripathy D. Actos Now for the prevention of diabetes (ACT NOW) study. BMC Endocr Disord. 2009 Jul 29;9:17. doi: 10.1186/1472-6823-9-17.
PubMed 19640291
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Actos Now for Prevention of Diabetes (ACT NOW)
- ClinicalTrials.gov ID
- NCT00220961
- Acronym / sponsor ID
- 02-062A
- Conditions
- Impaired Glucose Tolerance, Type 2 Diabetes
- Keywords
- Impaired Glucose Tolerance, Type 2 Diabetes, Prevention, Pioglitazone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 602 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- University of Texas, Takeda Pharmaceuticals North America, Inc.
- Study start
- Jan 2004
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Posted 11 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to examine whether pioglitazone versus placebo can reduce the conversion rate of impaired glucose tolerance (IGT) to type 2 diabetes mellitus
Detailed description
IGT is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, the hyperglycemia-related complications of this devastating disease can be prevented. Subjects with IGT will be identified with an oral glucose tolerance test (OGTT). Eligible subjects also will have a measurement of first phase insulin secretion and insulin sensitivity using the frequently sampled intravenous glucose tolerance test (FSIVGTT) and carotid intimal media thickness using carotid ultrasound. Following these measurements subjects will be randomized to receive pioglitazone or placebo and they will return every 3 months for determination of fasting plasma glucose (FPG) concentration and interim medical history. Recruitment will take place over 15 months. From the time that the recruitment period ends, subjects will be followed for a total of 24 months on pioglitazone or placebo. The OGTT will be repeated at 15,27, and 39 months, or if the FPG is ≥ 126 mg/dl on the 3-month follow up visits. If the diagnosis of diabetes is established before month 39 or at month 39, the FSIVGTT and carotid ultrasound will be repeated. At 39 months, subjects will be washed out of pioglitazone or placebo and the OGTT, FSIVGTT, and carotid ultrasound will be repeated at month 45.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablet similar to pioglitazone tablet |
| Pioglitazone | Active comparator | Drug: PioglitazonePioglitazone tablet similar to placebo tablet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Men and women
- All ethnic groups
- 18 years of age and older
- Impaired glucose tolerance by glucose tolerance test (fasting glucose 95-125 mg/dl and 2 hr glucose of 140-199 mg/dl)
- At least one of the following:
Key exclusion criteria (31 listed)
- Type 2 diabetes
- Previously treated with thiazolidinediones (ever) or metformin (within one year)
- Previously treated with a sulfonylurea, a meglitinide, an alpha glucosidase inhibitor for more than a week within last year or within the 3 months prior to randomization
- Previously treated with insulin (other than during pregnancy) for more than one week within the last year or within the 3 months prior to randomization
- Cardiovascular disease
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 |
|---|---|---|
| PioglitazoneAlso: ActosPioglitazone tablets - 45 mg/day | Drug | Pioglitazone |
| PlaceboPlacebo tablets similar to pioglitazone tablets - 1 tablet/day | Drug | Placebo |
Primary outcome
Prevention of Type 2 Diabetes
Time frame: 2.4 years
Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization
4 secondary outcomes
Change From Baseline in Fasting Plasma Glucose of 2.4 Years
Time frame: Baseline versus 2.4 years
Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test
Time frame: Baseline versus 2.4 years
Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values)
Time frame: Baseline versus 2.4 years
Change in Atherosclerosis
Time frame: Baseline versus 2.4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33210751Ipsen EO, Madsen KS, Chi Y, Pedersen-Bjergaard U, Richter B, Metzendorf MI, Hemmingsen B. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 19;11(11):CD013516. doi: 10.1002/14651858.CD013516.pub2.
- Derived from this study: PubMed 26982008Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Musi N, Reaven PD, DeFronzo RA. Diabetes Incidence and Glucose Tolerance after Termination of Pioglitazone Therapy: Results from ACT NOW. J Clin Endocrinol Metab. 2016 May;101(5):2056-62. doi: 10.1210/jc.2015-4202. Epub 2016 Mar 16.
- Derived from this study: PubMed 25603459Tripathy D, Cobb JE, Gall W, Adam KP, George T, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Reaven PD, Musi N, Ferrannini E, DeFronzo RA. A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study. J Clin Endocrinol Metab. 2015 May;100(5):1855-62. doi: 10.1210/jc.2014-3824. Epub 2015 Jan 20.
- Derived from this study: PubMed 24705615Tripathy D, Clement SC, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Gastaldelli A, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Musi N, Reaven PD, DeFronzo RA. Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW. Diabetes Care. 2014 Jun;37(6):1706-11. doi: 10.2337/dc13-1745. Epub 2014 Apr 4.
- Derived from this study: PubMed 23175674Saremi A, Schwenke DC, Buchanan TA, Hodis HN, Mack WJ, Banerji M, Bray GA, Clement SC, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Musi N, Tripathy D, DeFronzo RA, Reaven PD. Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):393-9. doi: 10.1161/ATVBAHA.112.300346. Epub 2012 Nov 21.
- Derived from this study: PubMed 21428766DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Hodis HN, Kitabchi AE, Mack WJ, Mudaliar S, Ratner RE, Williams K, Stentz FB, Musi N, Reaven PD; ACT NOW Study. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011 Mar 24;364(12):1104-15. doi: 10.1056/NEJMoa1010949.
- Derived from this study: PubMed 19640291Defronzo RA, Banerji M, Bray GA, Buchanan TA, Clement S, Henry RR, Kitabchi AE, Mudaliar S, Musi N, Ratner R, Reaven PD, Schwenke D, Stentz FB, Tripathy D. Actos Now for the prevention of diabetes (ACT NOW) study. BMC Endocr Disord. 2009 Jul 29;9:17. doi: 10.1186/1472-6823-9-17.
- American Diabetes AssociationLink provided by the sponsor.
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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.
Ralph A. DeFronzo, M.D. principal investigator
Texas Diabetes Institute
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pioglitazone in people with Impaired Glucose Tolerance and Type 2 Diabetes, run by The University of Texas Health Science Center at San Antonio at 8 sites in United States.
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 10 inclusion and 31 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: finished, as of the sponsor's last update on 11 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Prevention of Type 2 Diabetes (time frame: 2.4 years). 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 NCT00220961, which also lists 7 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 11 Aug 2016.