Diabetes Mellitus, Non-Insulin DependentPhase 2NCT00001870
Study of the Effects of Vitamin C on Patients With Type 2 Diabetes
A Phase 2 study testing Acetylcholine in people with Diabetes Mellitus, Non-Insulin Dependent and Non-Insulin Dependent, run by National Center for Complementary and Integrative Health (NCCIH) at 1 site in United States.
Trial summary
Diabetes is a disease characterized by decreased sensitivity to the action on insulin to promote sugar (glucose) use and blood vessel relaxation (vasodilation) in muscle. Insulin's ability to cause blood vessel relaxation is controlled, in part, by nitric oxide (NO). Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Non-Insulin Dependent, Non-Insulin Dependent
- What is being tested?
- Acetylcholine
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1999to Dec 2004
- Phase
- Phase 2
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- DIABETIC SUBJECTS:
- Males and non-pregnant females between the ages of 18 and 65 in good general health except for type 2 diabetes controlled with diet and/or oral hypoglycemic agents.
- Patients found to have plasma vitamin C levels less than 40 microliter M, will be enrolled into the protocol and taken off hypoglycemic agents approximately one week prior to each study.
- VITAMIN C-DEFICIENT CLINICAL RESEARCH VOLUNTEERS:
- Adults between the ages of 18 and 35 in good general health and on no drugs or medications.
Who cannot join
- ALL SUBJECTS:
- Pregnancy, liver disease, pulmonary disease, renal insufficiency, coronary heart disease, heart failure, peripheral vascular disease, coagulopathy, disease predisposing to vasculitis or Raynaud's phenomenon, bleeding disorders, kidney stones, glucose-6-phosphate dehydrogenase deficiency, family history of hemochromatosis/iron overload, platelet count less than 150,000/ml blood, prothrombin time/partial thromboplastin time (PT/PTT) greater than 1 second above the normal range, inability to give informed consent for all procedures, and positive tests for HIV, or hepatitis B or C.
- DIABETIC SUBJECTS:
- In addition, to the above exclusion criteria, the presence of proteinuria greater than 500 mg/24 hrs, proliferative retinipathy, or diabetic neuropathy
- VITAMIN C-DEFICIENT CLINICAL RESEARCH VOLUNTEERS:
- All the above exclusion criteria.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Center for Complementary and Alternative Medicine (NCCAM)
Bethesda, Maryland, 20892
About this study
Official title: An Exploratory Study of the Effects of Oral Vitamin C Administration on Insulin Sensitivity and Vascular Reactivity in Subjects With Type 2 Diabetes
Diabetes is a disease characterized by decreased sensitivity to the action on insulin to promote sugar (glucose) use and blood vessel relaxation (vasodilation) in muscle. Insulin's ability to cause blood vessel relaxation is controlled, in part, by nitric oxide (NO).
Nitric oxide is a substance produced by the cells lining blood vessel walls (endothelium). Increased blood flow to the muscle accounts for increased sugar (glucose) to areas of the body. Therefore, if the cells of blood vessel walls (endothelium) are not functioning properly it may contribute to insulin resistance.
Read more
Injections of Vitamin C directly into the arteries have been shown to improve blood vessel reaction to nitric oxide in diabetic patients. Researchers believe this may be due to Vitamin C's ability to increase the levels of nitric oxide in blood vessels.
The goal of this study is to determine the effects of vitamin C on both insulin sensitivity and endothelium function of patients with type 2 diabetes. An additional goal of the study is to determine the effects of vitamin C on patients with vitamin C deficiency.
Patients participating in this study will undergo a series of testes to determine insulin sensitivity and blood vessel reactivity. Patients will be divided into two groups. One group will receive doses of oral vitamin C. The other group will receive doses of a placebo (inactive pill not containing vitamin C). Patients will receive the medications for four weeks and then be tested again for insulin sensitivity and blood vessel reactivity.
Researchers believe that doses of vitamin C in diabetics or patients with vitamin C deficiency will improve insulin sensitivity and function of endothelium. Results gathered form this study may provide information about vitamin C levels in diabetics and may lead to the development of new therapies to treat insulin resistance and endothelium dysfunction.
Read the detailed description
Diabetes is characterized by decreased sensitivity to the actions of insulin to promote both glucose utilization and vasodilation in skeletal muscle beds. Insulin's vasodilator action is mediated, in part, by endothelial-derived nitric oxide (NO). Increased blood flow accounts for approximately 25% of the increase in skeletal muscle glucose disposal mediated by insulin. Therefore, endothelial dysfunction may contribute to insulin resistance. Intraarterial administration of vitamin C improves NO-dependent vascular reactivity in diabetic subjects (but not normal subjects). This may be due to antioxidant properties of vitamin C that result in relative increases in the level of NO in the diabetic vasculature. In this exploratory protocol, our primary objective is to assess the effects of oral administration of vitamin C on both insulin sensitivity and endothelial function in subjects with type 2 diabetes. A secondary, peripheral objective, is to study these effects in vitamin C-deficient clinical research volunteers. Hyperinsulinemic euglycemic glucose clamp procedures and forearm blood flow measurements will be used to assess both insulin sensitivity and vascular reactivity in diabetic subjects and clinical research volunteers who have plasma vitamin C levels less than 30 microM. The subjects will then be given either placebo or oral vitamin C supplementation (800 mg/day) for four weeks and assessment of insulin sensitivity and vascular reactivity will be repeated. Plasma levels of vitamin C will be measured to confirm that subjects in the experimental group have an appropriate increase in vitamin C levels. We hypothesize that chronic oral administration of vitamin C to diabetic or clinical research volunteers who are deficient in vitamin C will improve insulin sensitivity and endothelial function. Our study will provide information about vitamin C levels in diabetic subjects and may suggest a potential therapy to significantly improve endothelial dysfunction and insulin resistance.
- Being tested
- Acetylcholine
- Keywords
- Insulin Resistance, Oxidative Stress, Antioxidant, Endothelial Function, Glucose Clamp, Type 2 Diabetes, Vitamin C Deficiency
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance, Ascorbic Acid Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetylcholineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startJan 1999
- Study completionDec 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Non-Insulin DependentStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Enrolment
- 150 participants
Sponsor and investigators
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001870
- Sponsor's protocol ID
- 990033
- Other IDs
- 99-AT-0033
- Status last verified
- Dec 2004
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet. 1992 Oct 17;340(8825):925-9. doi: 10.1016/0140-6736(92)92814-v.
PubMed 1357346DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988 Jun;37(6):667-87. doi: 10.2337/diab.37.6.667. No abstract available.
PubMed 3289989Lillioja S, Mott DM, Howard BV, Bennett PH, Yki-Jarvinen H, Freymond D, Nyomba BL, Zurlo F, Swinburn B, Bogardus C. Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians. N Engl J Med. 1988 May 12;318(19):1217-25. doi: 10.1056/NEJM198805123181901.
PubMed 3283552
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study of the Effects of Oral Vitamin C Administration on Insulin Sensitivity and Vascular Reactivity in Subjects With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00001870
- Acronym / sponsor ID
- 990033
- Keywords
- Insulin Resistance, Oxidative Stress, Antioxidant, Endothelial Function, Glucose Clamp, Type 2 Diabetes, Vitamin C Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)US National Institutes of Health
- Study start
- Jan 1999
- Study completion
- Dec 2004
- First posted
- 4 Nov 1999 (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.
Diabetes is a disease characterized by decreased sensitivity to the action on insulin to promote sugar (glucose) use and blood vessel relaxation (vasodilation) in muscle. Insulin's ability to cause blood vessel relaxation is controlled, in part, by nitric oxide (NO).
Nitric oxide is a substance produced by the cells lining blood vessel walls (endothelium). Increased blood flow to the muscle accounts for increased sugar (glucose) to areas of the body. Therefore, if the cells of blood vessel walls (endothelium) are not functioning properly it may contribute to insulin resistance.
Injections of Vitamin C directly into the arteries have been shown to improve blood vessel reaction to nitric oxide in diabetic patients. Researchers believe this may be due to Vitamin C's ability to increase the levels of nitric oxide in blood vessels.
The goal of this study is to determine the effects of vitamin C on both insulin sensitivity and endothelium function of patients with type 2 diabetes. An additional goal of the study is to determine the effects of vitamin C on patients with vitamin C deficiency.
Patients participating in this study will undergo a series of testes to determine insulin sensitivity and blood vessel reactivity. Patients will be divided into two groups. One group will receive doses of oral vitamin C. The other group will receive doses of a placebo (inactive pill not containing vitamin C). Patients will receive the medications for four weeks and then be tested again for insulin sensitivity and blood vessel reactivity.
Researchers believe that doses of vitamin C in diabetics or patients with vitamin C deficiency will improve insulin sensitivity and function of endothelium. Results gathered form this study may provide information about vitamin C levels in diabetics and may lead to the development of new therapies to treat insulin resistance and endothelium dysfunction.
Detailed description
Diabetes is characterized by decreased sensitivity to the actions of insulin to promote both glucose utilization and vasodilation in skeletal muscle beds. Insulin's vasodilator action is mediated, in part, by endothelial-derived nitric oxide (NO). Increased blood flow accounts for approximately 25% of the increase in skeletal muscle glucose disposal mediated by insulin. Therefore, endothelial dysfunction may contribute to insulin resistance. Intraarterial administration of vitamin C improves NO-dependent vascular reactivity in diabetic subjects (but not normal subjects). This may be due to antioxidant properties of vitamin C that result in relative increases in the level of NO in the diabetic vasculature. In this exploratory protocol, our primary objective is to assess the effects of oral administration of vitamin C on both insulin sensitivity and endothelial function in subjects with type 2 diabetes. A secondary, peripheral objective, is to study these effects in vitamin C-deficient clinical research volunteers. Hyperinsulinemic euglycemic glucose clamp procedures and forearm blood flow measurements will be used to assess both insulin sensitivity and vascular reactivity in diabetic subjects and clinical research volunteers who have plasma vitamin C levels less than 30 microM. The subjects will then be given either placebo or oral vitamin C supplementation (800 mg/day) for four weeks and assessment of insulin sensitivity and vascular reactivity will be repeated. Plasma levels of vitamin C will be measured to confirm that subjects in the experimental group have an appropriate increase in vitamin C levels. We hypothesize that chronic oral administration of vitamin C to diabetic or clinical research volunteers who are deficient in vitamin C will improve insulin sensitivity and endothelial function. Our study will provide information about vitamin C levels in diabetic subjects and may suggest a potential therapy to significantly improve endothelial dysfunction and insulin resistance.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Males and non-pregnant females between the ages of 18 and 65 in good general health except for type 2 diabetes controlled with diet and/or oral hypoglycemic agents.
- Patients found to have plasma vitamin C levels less than 40 microliter M, will be enrolled into the protocol and taken off hypoglycemic agents approximately one week prior to each study.
- Adults between the ages of 18 and 35 in good general health and on no drugs or medications.
Key exclusion criteria (6 listed)
- Pregnancy, liver disease, pulmonary disease, renal insufficiency, coronary heart disease, heart failure, peripheral vascular disease, coagulopathy, disease predisposing to vasculitis or Raynaud's phenomenon, bleeding disorders, kidney stones, glucose-6-phosphate dehydrogenase deficiency, family history of hemochromatosis/iron overload, platelet count less than 150,000/ml blood, prothrombin time/partial thromboplastin time (PT/PTT) greater than 1 second above the normal range, inability to give informed consent for all procedures, and positive tests for HIV, or hepatitis B or C.
- In addition, to the above exclusion criteria, the presence of proteinuria greater than 500 mg/24 hrs, proliferative retinipathy, or diabetic neuropathy
- All the above exclusion criteria.
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 |
|---|---|---|
| Acetylcholine | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 1357346Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet. 1992 Oct 17;340(8825):925-9. doi: 10.1016/0140-6736(92)92814-v.
- Background: PubMed 3289989DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988 Jun;37(6):667-87. doi: 10.2337/diab.37.6.667. No abstract available.
- Background: PubMed 3283552Lillioja S, Mott DM, Howard BV, Bennett PH, Yki-Jarvinen H, Freymond D, Nyomba BL, Zurlo F, Swinburn B, Bogardus C. Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians. N Engl J Med. 1988 May 12;318(19):1217-25. doi: 10.1056/NEJM198805123181901.
Related trials for Diabetes Mellitus, Non-Insulin Dependent
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acetylcholine in people with Diabetes Mellitus, Non-Insulin Dependent and Non-Insulin Dependent, run by National Center for Complementary and Integrative Health (NCCIH) at 1 site 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 5 inclusion and 6 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 4 Mar 2008. 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 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001870, which also lists 3 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 4 Mar 2008.