Type 2 DiabetesPhase 1NCT01238224
Effects of PDE-5 Inhibition on Postprandial Hyperglycemia in Type 2 Diabetes
A Phase 1 study testing Tadalafil in people with Type 2 Diabetes, run by Vastra Gotaland Region at 1 site in Sweden.
Trial summary
An increase of blood flow and capillary permeability decrease the impact of an endothelial barrier for glucose and insulin allowing them to reach their target cells in peripheral insulin sensitive organ in the human body. Read more about this study
- Who is it for?
- Ages 40 to 65 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Tadalafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteSweden
- Study dates
- Nov 2009to Nov 2011
- Phase
- Phase 1
- 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 40 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal state, defines as natural amenorrhea for at least 12 months.
- Age; females 52-65 years, males: 40-65 years.
- Type 2 diabetes based on fasting plasma glucose or 2-hr glucose after an OGTT.
- Diabetes duration less than 5 years.
Who cannot join
- Patients with concurrent use of nitrates or NO donors, history of heart or cerebrovascular disease, cardiac failure (stages NYHA II-IV), uncontrolled hypertension (> 160/100 mm Hg), significant diabetic complications, and inadequate glycemic control (HbA1c > 7%, ref value 3.5-5.3%)
- Patients on glitazones, insulin, beta-blockers, ACE-inhibitors and corticosteroids
Trial locations and contacts
1 site in 1 country.
Sweden1 site
The Wallenberg Laboratory, Dept of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Bruna stråket 16,
Gothenburg, SE 413 45
About this study
Official title: The Effect of Selective PDE-5 Inhibition on Capillary Recruitment, Glucose Uptake and Endothelial Function Following a Mixed Meal in Patients With Type 2 Diabetes Patients.
An increase of blood flow and capillary permeability decrease the impact of an endothelial barrier for glucose and insulin allowing them to reach their target cells in peripheral insulin sensitive organ in the human body. It is well known that insulin-resistant type 2 diabetes patients have an impaired blood flow in skeletal muscle and it is therefore important to elucidate means to reverse this metabolic defect.
The investigators have in a recently published study in type 2 diabetes patients used a drug against erectile dysfunction, the PDE-5 inhibitor tadalafil, with known effects on several vascular territories, to increase muscle blood flow in type 2 diabetes patients who were studied after fasting overnight.
The aim of this study is to test the hypothesis that tadalafil, compared to placebo, increases muscle glucose uptake and lowers blood glucose following a mixed meal served to type 2 diabetes patients.
Read the detailed description
An increase of blood flow and capillary permeability decrease the impact of an endothelial barrier for glucose and insulin allowing them to reach their target cells in peripheral insulin sensitive organ in the human body. It is well known that insulin-resistant type 2 diabetes patients have an impaired blood flow in skeletal muscle and it is therefore important to elucidate means to reverse this metabolic defect.
The investigators have in a recently published study in type 2 diabetes patients used a drug against erectile dysfunction, the PDE-5 inhibitor tadalafil, with known effects on several vascular territories, to increase muscle blood flow in type 2 diabetes patients who were studied after fasting overnight. In fact, the investigators observed that tadalafil compared to placebo increased glucose uptake in muscle in parallel with an augmented capillary recruitment in muscle. This was the first publication to show that the pharmacological principle to inhibit the enzyme phosphodiesterase-5 (PDE-5) may mediate an increased muscle glucose uptake and, hence, may be a novel strategy to lower blood glucose in type 2 diabetes patients.
The aim of this study is to test the hypothesis that tadalafil, compared to placebo, increases muscle glucose uptake and lowers blood glucose following a mixed meal served to type 2 diabetes patients.
- Conditions
- Type 2 Diabetes
- Being tested
- Tadalafil
- Keywords
- Insulin resistance, Phosphodiesterase-5 inhibition, Microdialysis, Type 2 diabetes, Endothelial dysfunction, Oral hypoglycaemic agents
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Also called Cialis
This is an acute study. Tadalafil 20 mg administered prior to a meal
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | A single dose of placebo is administered 30 min before a mixed meal. Receives: Drug: Tadalafil |
| Tadalafil | Active comparator | A single dose of tadalafil 20 mg is administered 30 min before a mixed meal. Receives: Drug: Tadalafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Capillary recruitment, muscle glucose uptake and circulating glucose levels following a meal
Capillary recruitment and glucose uptake in forearm muscle as well as circulating glucose levels following acute administration of tadalafil or placebo in type 2 diabetes patients.
Measured: Five hours after a mixed meal
Secondary outcomes (1)
Vascular function and circulating biomarkers.
Arterial stiffness as measured by pulse wave velocity and circulating concentrations of metabolic variables
Measured: Five hours after a mixed meal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2010 (estimated)
- Study startNov 2009
- Primary completionNov 2011
- Study completionNov 2011
Why it stopped: Durability of study medications could not be guaranteed after the expire date.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Vastra Gotaland RegionThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Per-Anders Jansson, MD, PhD, Principal investigator, Region of Västra Götaland, Sahlgrenska University Hospital/Sahlgrenska University at University of Göteborg, Dept of Molecular and Clinical Medicine, SE 413 45 Göteborg, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01238224
- Sponsor's protocol ID
- 2007-003921-25
- Status last verified
- Jun 2015
- First submitted
- 6 Oct 2010
- Last updated
- 12 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Jansson PA, Murdolo G, Sjogren L, Nystrom B, Sjostrand M, Strindberg L, Lonnroth P. Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes. Diabetologia. 2010 Oct;53(10):2205-8. doi: 10.1007/s00125-010-1819-4. Epub 2010 Jun 10.
PubMed 20535445
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Selective PDE-5 Inhibition on Capillary Recruitment, Glucose Uptake and Endothelial Function Following a Mixed Meal in Patients With Type 2 Diabetes Patients.
- ClinicalTrials.gov ID
- NCT01238224
- Acronym / sponsor ID
- 2007-003921-25
- Conditions
- Type 2 Diabetes
- Keywords
- Insulin resistance, Phosphodiesterase-5 inhibition, Microdialysis, Type 2 diabetes, Endothelial dysfunction, Oral hypoglycaemic agents
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Durability of study medications could not be guaranteed after the expire date.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Vastra Gotaland RegionOther government
- Study start
- Nov 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 10 Nov 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.
An increase of blood flow and capillary permeability decrease the impact of an endothelial barrier for glucose and insulin allowing them to reach their target cells in peripheral insulin sensitive organ in the human body. It is well known that insulin-resistant type 2 diabetes patients have an impaired blood flow in skeletal muscle and it is therefore important to elucidate means to reverse this metabolic defect.
The investigators have in a recently published study in type 2 diabetes patients used a drug against erectile dysfunction, the PDE-5 inhibitor tadalafil, with known effects on several vascular territories, to increase muscle blood flow in type 2 diabetes patients who were studied after fasting overnight.
The aim of this study is to test the hypothesis that tadalafil, compared to placebo, increases muscle glucose uptake and lowers blood glucose following a mixed meal served to type 2 diabetes patients.
Detailed description
An increase of blood flow and capillary permeability decrease the impact of an endothelial barrier for glucose and insulin allowing them to reach their target cells in peripheral insulin sensitive organ in the human body. It is well known that insulin-resistant type 2 diabetes patients have an impaired blood flow in skeletal muscle and it is therefore important to elucidate means to reverse this metabolic defect.
The investigators have in a recently published study in type 2 diabetes patients used a drug against erectile dysfunction, the PDE-5 inhibitor tadalafil, with known effects on several vascular territories, to increase muscle blood flow in type 2 diabetes patients who were studied after fasting overnight. In fact, the investigators observed that tadalafil compared to placebo increased glucose uptake in muscle in parallel with an augmented capillary recruitment in muscle. This was the first publication to show that the pharmacological principle to inhibit the enzyme phosphodiesterase-5 (PDE-5) may mediate an increased muscle glucose uptake and, hence, may be a novel strategy to lower blood glucose in type 2 diabetes patients.
The aim of this study is to test the hypothesis that tadalafil, compared to placebo, increases muscle glucose uptake and lowers blood glucose following a mixed meal served to type 2 diabetes patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: TadalafilA single dose of placebo is administered 30 min before a mixed meal. |
| Tadalafil | Active comparator | Drug: TadalafilA single dose of tadalafil 20 mg is administered 30 min before a mixed meal. |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Postmenopausal state, defines as natural amenorrhea for at least 12 months.
- Age; females 52-65 years, males: 40-65 years.
- Type 2 diabetes based on fasting plasma glucose or 2-hr glucose after an OGTT.
- Diabetes duration less than 5 years.
Key exclusion criteria (2 listed)
- Patients with concurrent use of nitrates or NO donors, history of heart or cerebrovascular disease, cardiac failure (stages NYHA II-IV), uncontrolled hypertension (> 160/100 mm Hg), significant diabetic complications, and inadequate glycemic control (HbA1c > 7%, ref value 3.5-5.3%)
- Patients on glitazones, insulin, beta-blockers, ACE-inhibitors and corticosteroids
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 |
|---|---|---|
| TadalafilAlso: CialisThis is an acute study. Tadalafil 20 mg administered prior to a meal | Drug | Placebo, Tadalafil |
Primary outcome
Capillary recruitment, muscle glucose uptake and circulating glucose levels following a meal
Time frame: Five hours after a mixed meal
Capillary recruitment and glucose uptake in forearm muscle as well as circulating glucose levels following acute administration of tadalafil or placebo in type 2 diabetes patients.
1 secondary outcome
Vascular function and circulating biomarkers.
Time frame: Five hours after a mixed meal
Results and safety
The study was stopped early (reason given: Durability of study medications could not be guaranteed after the expire date.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2020.
- Background: PubMed 20535445Jansson PA, Murdolo G, Sjogren L, Nystrom B, Sjostrand M, Strindberg L, Lonnroth P. Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes. Diabetologia. 2010 Oct;53(10):2205-8. doi: 10.1007/s00125-010-1819-4. Epub 2010 Jun 10.
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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.
Per-Anders Jansson, MD, PhD principal investigator
Region of Västra Götaland, Sahlgrenska University Hospital/Sahlgrenska University at University of Göteborg, Dept of Molecular and Clinical Medicine, SE 413 45 Göteborg, Sweden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tadalafil in people with Type 2 Diabetes, run by Vastra Gotaland Region at 1 site in Sweden.
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 4 inclusion and 2 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: stopped early, as of the sponsor's last update on 12 Feb 2020. 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 Sweden. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: Durability of study medications could not be guaranteed after the expire date.). Results are not available in the source record.
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?
Capillary recruitment, muscle glucose uptake and circulating glucose levels following a meal (time frame: Five hours after a mixed meal). 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 NCT01238224, which also lists 1 linked publication.
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 12 Feb 2020.