Type 2 DiabetesPhase 4NCT01056497
The Effect of A-lipoic Acid (ALA) on Fatty Acid-induced Impairment of Glucose-stimulated Insulin Secretion
A Phase 4 study testing alpha lipoic acid in people with Type 2 Diabetes and Prediabetes, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Chronically elevated free fatty acids impair insulin sensitivity and insulin secretion (ie lipotoxicity) by a combination of oxidative stress, endoplasmic reticulum (ER) stress and inflammation. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes, Prediabetes
- What is being tested?
- alpha lipoic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2010to Jun 2011
- Phase
- Phase 4
- 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 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women aged 20-65 years:
- Written informed consent obtained
- Body mass index (BMI) > 27kg/m2
- Glucose tolerance test may be normal or demonstrate impaired glucose tolerance but not frank diabetes
- Hemoglobin above 130g/L
Who cannot join
- Subject has a history of hepatitis/hepatic disease that has been active within the previous two years
- Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP > 100 or systolic > 180) or proliferative retinopathy
- Type 2 diabetes by history or OGTT
- Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure
- Any laboratory values: AST > 2x ULN; ALT > 2x ULN; TSH > 6 mU/l
- A history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions. History of hypersensitivity to heparin
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- Current addiction to alcohol or substances of abuse as determined by the investigator
- Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
- Any lipid lowering of hypoglycemic agents
- Previous history of asthma
- Will not donate blood three months prior to and three months post study procedures
- Thrombocytopenia
Trial locations and contacts
1 site in 1 country.
About this study
Chronically elevated free fatty acids impair insulin sensitivity and insulin secretion (ie lipotoxicity) by a combination of oxidative stress, endoplasmic reticulum (ER) stress and inflammation. This study will test whether alpha-lipoic acid, which has potent antioxidant and anti-inflammatory properties, prevents or ameliorates lipotoxicity.
Read the detailed description
Alpha-Lipoic Acid (ALA) is a naturally occurring dithiol compound absorbed intact from dietary sources and synthesized enzymatically in the mitochondrion from octanoic acid. It serves a critical role in mitochondrial energy metabolism and is a potent biological antioxidant. It is widely available as an over-the-counter health supplement. It has generated considerable interest among the lay public and the research community for the use of ALA as a nutritive supplement and as a pharmacotherapy for diabetes and many other disorders. There is growing evidence that ALA has beneficial effects on the treatment of type 2 diabetes (T2DM) and some of its complications. It represents an attractive pharmacological target in the treatment of T2DM by modulating the signal transduction pathways in insulin resistance and antagonizing the oxidative and inflammatory stresses, which are major pathways in the pathogenesis of this disorder. Chronic elevation of plasma FFAs are believed to contribute to insulin resistance and defects in insulin secretion by promoting oxidative stress and inflammation. A potent antioxidant and free radical scavenger, ALA also targets cellular signal transduction pathways, which increases glucose uptake and utilization, thus providing specific targeted therapy in the treatment of insulin resistance. ALA has been shown to be safe when taken in high doses (2400mg/d) for prolonged time periods (6 months and longer), even in patients with renal and liver failure. In fact no upper limit for ALA consumption in humans has been established.
- Each subject will undergo 4 studies, 4 to 6 weeks apart. Each study will consist of a 2 week treatment period with either oral ALA tablets or placebo tablets, followed by 30 hour hospital stay to infuse lipid or saline and to test insulin sensitivity and insulin secretion.
- The study will be conducted as a single blind study, with the subject not knowing whether they are receiving a placebo or ALA. For safety reasons and since it will not influence the results of this study it will not be conducted as a double blind study.
- On each of four occasions, 4 weeks apart, after taking the tablets for 2 weeks, the subject will fast overnight for 12-hours prior to their admission to the Toronto General Hospital metabolic research ward for 30 hours to undergo testing as follows. The four studies will be conducted in random order:
- Conditions
- Type 2 Diabetes, Prediabetes
- Being tested
- alpha lipoic acid
- Keywords
- diabetes, alpha lipoic acid, endoplasmic reticulum (ER) stress, insulin secretion, insulin sensitivity
- Medical subject headings
- Diabetes Mellitus, Type 2, Prediabetic State, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alpha lipoic acidDrug
Also called lipoic acid, ALA
A 2 week treatment period with either oral ALA tablets or placebo tablets, followed by 30 hour hospital stay to infuse lipid or saline and to test insulin sensitivity and insulin secretion. For two weeks prior to each admission to hospital and during each hospital admission subjects will ingest 3 tablets 2 times per day with breakfast and supper, 1800mg per day
| Study group | Role | What they receive |
|---|---|---|
| alpha lipoic acid | Experimental | Not described Receives: Drug: alpha lipoic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
insulin secretion and insulin sensitivity To determine whether ALA ameliorates or prevents impairment of insulin secretion and insulin sensi
Measured: 6 months
Secondary outcomes (1)
To determine the role of oxidative stress and inflammation in the pathogenesis of lipotoxicity
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2010 (estimated)
- Study startFeb 2010
- Primary completionJan 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Diabetes Association
- Responsible party
- Principal investigator, Gary Lewis, University Health Network, Toronto
- Investigators
- gary F Lewis, MD, Principal investigator, University Health Network, Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01056497
- Sponsor's protocol ID
- 090818B
- Other IDs
- Canadian Diabetes Association
- Status last verified
- Sep 2012
- First submitted
- 17 Dec 2009
- Last updated
- 2 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of A-lipoic Acid (ALA) on Fatty Acid-induced Impairment of Glucose-stimulated Insulin Secretion
- ClinicalTrials.gov ID
- NCT01056497
- Acronym / sponsor ID
- 090818B
- Conditions
- Type 2 Diabetes, Prediabetes
- Keywords
- diabetes, alpha lipoic acid, endoplasmic reticulum (ER) stress, insulin secretion, insulin sensitivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Canadian Diabetes Association
- Study start
- Feb 2010
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 26 Jan 2010 (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.
Chronically elevated free fatty acids impair insulin sensitivity and insulin secretion (ie lipotoxicity) by a combination of oxidative stress, endoplasmic reticulum (ER) stress and inflammation. This study will test whether alpha-lipoic acid, which has potent antioxidant and anti-inflammatory properties, prevents or ameliorates lipotoxicity.
Detailed description
Alpha-Lipoic Acid (ALA) is a naturally occurring dithiol compound absorbed intact from dietary sources and synthesized enzymatically in the mitochondrion from octanoic acid. It serves a critical role in mitochondrial energy metabolism and is a potent biological antioxidant. It is widely available as an over-the-counter health supplement. It has generated considerable interest among the lay public and the research community for the use of ALA as a nutritive supplement and as a pharmacotherapy for diabetes and many other disorders. There is growing evidence that ALA has beneficial effects on the treatment of type 2 diabetes (T2DM) and some of its complications. It represents an attractive pharmacological target in the treatment of T2DM by modulating the signal transduction pathways in insulin resistance and antagonizing the oxidative and inflammatory stresses, which are major pathways in the pathogenesis of this disorder. Chronic elevation of plasma FFAs are believed to contribute to insulin resistance and defects in insulin secretion by promoting oxidative stress and inflammation. A potent antioxidant and free radical scavenger, ALA also targets cellular signal transduction pathways, which increases glucose uptake and utilization, thus providing specific targeted therapy in the treatment of insulin resistance. ALA has been shown to be safe when taken in high doses (2400mg/d) for prolonged time periods (6 months and longer), even in patients with renal and liver failure. In fact no upper limit for ALA consumption in humans has been established.
- Each subject will undergo 4 studies, 4 to 6 weeks apart. Each study will consist of a 2 week treatment period with either oral ALA tablets or placebo tablets, followed by 30 hour hospital stay to infuse lipid or saline and to test insulin sensitivity and insulin secretion.
- The study will be conducted as a single blind study, with the subject not knowing whether they are receiving a placebo or ALA. For safety reasons and since it will not influence the results of this study it will not be conducted as a double blind study.
- On each of four occasions, 4 weeks apart, after taking the tablets for 2 weeks, the subject will fast overnight for 12-hours prior to their admission to the Toronto General Hospital metabolic research ward for 30 hours to undergo testing as follows. The four studies will be conducted in random order:
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| alpha lipoic acid | Experimental | Drug: alpha lipoic acid |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent obtained
- Body mass index (BMI) > 27kg/m2
- Glucose tolerance test may be normal or demonstrate impaired glucose tolerance but not frank diabetes
- Hemoglobin above 130g/L
Key exclusion criteria (12 listed)
- Subject has a history of hepatitis/hepatic disease that has been active within the previous two years
- Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP > 100 or systolic > 180) or proliferative retinopathy
- Type 2 diabetes by history or OGTT
- Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure
- Any laboratory values: AST > 2x ULN; ALT > 2x ULN; TSH > 6 mU/l
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 |
|---|---|---|
| alpha lipoic acidAlso: lipoic acid, ALAA 2 week treatment period with either oral ALA tablets or placebo tablets, followed by 30 hour hospital stay to infuse lipid or saline and to test insulin sensitivity and insulin secretion. For two weeks prior to each admission to hospital and during each hospital admission subjects will ingest 3 tablets 2 times per day with breakfast and supper, 1800mg per day | Drug | alpha lipoic acid |
Primary outcome
insulin secretion and insulin sensitivity To determine whether ALA ameliorates or prevents impairment of insulin secretion and insulin sensi
Time frame: 6 months
1 secondary outcome
To determine the role of oxidative stress and inflammation in the pathogenesis of lipotoxicity
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2012.
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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.
gary F Lewis, MD principal investigator
University Health Network, Toronto General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing alpha lipoic acid in people with Type 2 Diabetes and Prediabetes, run by University Health Network, Toronto at 1 site in Canada.
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 5 inclusion and 12 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 2 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
insulin secretion and insulin sensitivity To determine whether ALA ameliorates or prevents impairment of insulin secretion and insulin sensi (time frame: 6 months). 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 2 Oct 2012.