ObesityPhase 4NCT02524184
Sildenafil Activates Browning of White Adipose and Improves Insulin Sensitivity
A Phase 4 study testing sildenafil in people with Obesity, run by Xiang Guang-da at 1 site in China.
Trial summary
Obesity and metabolic disease result when energy intake consistently exceeds energy expenditure. One appealing new target for treatment is the activation of brown adipose tissue (BAT), an organ recently found to be functional in adult humans. Read more about this study
- Who is it for?
- Ages 20 to 30 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- sildenafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteChina
- Study dates
- Aug 2015to Sep 2016
- 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 30 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- overweight volunteers
- 20-30 years old
- body mass index >=25 kg/m2
- normal glucose tolerance
Who cannot join
- normal body mass index
- abnormal cardiovascular status
- women
- history of any local or systemic infectious disease with fever or requiring antibiotic within four weeks of drug administration
- current addiction to alcohol or substances of abuse
- children
Show all 10Show fewer
- current addiction to alcohol or substances of abuse
- mental incapacity
- the use of any medication within four weeks
- subjects with hyperthyroidism or hypothyroidism, hypertension (even if controlled with medications)
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Wuhan General Hospital
Wuhan, Hubei, 430070
Guangda Xiang, MD, 13517275283, Guangda64@hotmail.com
Lin Xiang, MD, 18627838901, xianglin832010@hotmail.com
About this study
Official title: Sildenafil Activates Browning of White Adipose and Improves Insulin Sensitivity in Human Adults
Obesity and metabolic disease result when energy intake consistently exceeds energy expenditure. One appealing new target for treatment is the activation of brown adipose tissue (BAT), an organ recently found to be functional in adult humans. Brown adipocytes selectively express uncoupling protein 1 (UCP1), which renders the inner membrane of mitochondria leaky, thereby diverting chemical energy from ATP generation to heat production. Interest in BAT has been spurred by the recognition that in addition to classical BAT depots, other brown-fat-like cells are present in the subcutaneous white adipose tissue (WAT) in animals and also in humans.These cells have structural and functional properties that resemble brown adipocytes, and they are referred to as beige or 'brite' (brown-in-white) adipocytes. Interestingly, browning of WAT can be induced in animals and humans by physiological stimuli such as cold exposure, which increases adrenergic tone, and by exercise, which selectively drives WAT browning through irisin, an exercise-induced myokine. In addition b-adrenergic drugs and other pharmacological agents,such as prostaglandins, can induce browning of white adipose tissue. More recently, one study showed that treatment of C57BL/6 mice with phosphodiesterase inhibitor sildenafil (12 mg/kg/d) for 7 d caused 4.6-fold increase in uncoupling protein-1 expression and promoted establishment of a brown fat cell-like phenotype ("browning") of WAT in vivo. Therefore, the investigators hypothesized that sildenafil can promote browning of white adipose tissue and improves insulin sensitivity in human adults.
Read the detailed description
The study subjects will be taken placebo (first stage) and sildenafil (second stage) intervention for 7 days, respectively afterward.Subcutaneous fat tissue and muscle samples will be obtained by biopsy from some individuals and measure the browning of white adipose tissue and insulin signaling.The insulin sensitivity will be tested by insulin clamp assay before and after each intervention, respectively. In addition,blood samples for biochemical analysis will be obtained before and after each intervention, respectively.
The browning of white adipose tissue will be measured by the expressions of peroxisome proliferator-activated receptor-γ (PPARγ), PPARγcoactivator 1α (PGC-1α), uncoupling protein 1 (UCP-1), the second messenger cyclic guanosine-3', 5'-monophosphate (cGMP),PR domain containing 16 zinc finger transcription factor (Prdm16) and deiodinase, iodothyronine, type II (DIO2).The metabolic makers will be measured by blood pressure, heart rate, thyroid functions, resting metabolic rate, respiratory quotient, blood cGMP, blood insulin and blood glucose.
- Conditions
- Obesity
- Being tested
- sildenafil, placebo
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sildenafilDrug
sildenafil 100 mg per day for 7 days.
placeboDrug
an identical placebo per day for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Experimental | Eleven patients receive sildenafil 100mg/day (25 mg at 8 AM plus 25 mg at 4 PM plus 50 mg at 10 PM)for 7 days. Receives: Drug: sildenafil |
| Placebo group | Placebo comparator | An identical placebo for 7 days in placebo group. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Browning of white adipose tissue
The browning of white adipose tissue was measured by Western blot (including the expressions of peroxisome proliferator-activated receptor-γ (PPARγ), PPARγcoactivator 1α (PGC-1α), uncoupling protein 1 (UCP-1), the second messenger cyclic guanosine-3', 5'-monophosphate (cGMP),PR domain containing 16 zinc finger transcription factor (Prdm16) and deiodinase, iodothyronine, type II (DIO2)).
Measured: 7 days
Secondary outcomes (1)
Improvement of insulin sensitivity
The insulin sensitivity will be tested by insulin clamp before and after each intervention,respectively.
Measured: 7days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2015 (estimated)
- Study startAug 2015
- Primary completionSep 2016 (estimated)
- Study completionSep 2016 (estimated)
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 ObesityStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiang Guang-da
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xiang Guang-da, Wuhan General Hospital of Guangzhou Military Command
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02524184
- Sponsor's protocol ID
- Wze20150088
- Status last verified
- Aug 2016
- First submitted
- 2 Aug 2015
- Last updated
- 2 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li S, Li Y, Xiang L, Dong J, Liu M, Xiang G. Sildenafil induces browning of subcutaneous white adipose tissue in overweight adults. Metabolism. 2018 Jan;78:106-117. doi: 10.1016/j.metabol.2017.09.008. Epub 2017 Oct 3.
PubMed 28986166
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sildenafil Activates Browning of White Adipose and Improves Insulin Sensitivity in Human Adults
- ClinicalTrials.gov ID
- NCT02524184
- Acronym / sponsor ID
- Wze20150088
- Conditions
- Obesity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 11 participants (estimated)
- Lead sponsor
- Xiang Guang-daUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- Sep 2016 (estimated)
- Study completion
- Sep 2016 (estimated)
- First posted
- 14 Aug 2015 (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.
Obesity and metabolic disease result when energy intake consistently exceeds energy expenditure. One appealing new target for treatment is the activation of brown adipose tissue (BAT), an organ recently found to be functional in adult humans. Brown adipocytes selectively express uncoupling protein 1 (UCP1), which renders the inner membrane of mitochondria leaky, thereby diverting chemical energy from ATP generation to heat production. Interest in BAT has been spurred by the recognition that in addition to classical BAT depots, other brown-fat-like cells are present in the subcutaneous white adipose tissue (WAT) in animals and also in humans.These cells have structural and functional properties that resemble brown adipocytes, and they are referred to as beige or 'brite' (brown-in-white) adipocytes. Interestingly, browning of WAT can be induced in animals and humans by physiological stimuli such as cold exposure, which increases adrenergic tone, and by exercise, which selectively drives WAT browning through irisin, an exercise-induced myokine. In addition b-adrenergic drugs and other pharmacological agents,such as prostaglandins, can induce browning of white adipose tissue. More recently, one study showed that treatment of C57BL/6 mice with phosphodiesterase inhibitor sildenafil (12 mg/kg/d) for 7 d caused 4.6-fold increase in uncoupling protein-1 expression and promoted establishment of a brown fat cell-like phenotype ("browning") of WAT in vivo. Therefore, the investigators hypothesized that sildenafil can promote browning of white adipose tissue and improves insulin sensitivity in human adults.
Detailed description
The study subjects will be taken placebo (first stage) and sildenafil (second stage) intervention for 7 days, respectively afterward.Subcutaneous fat tissue and muscle samples will be obtained by biopsy from some individuals and measure the browning of white adipose tissue and insulin signaling.The insulin sensitivity will be tested by insulin clamp assay before and after each intervention, respectively. In addition,blood samples for biochemical analysis will be obtained before and after each intervention, respectively.
The browning of white adipose tissue will be measured by the expressions of peroxisome proliferator-activated receptor-γ (PPARγ), PPARγcoactivator 1α (PGC-1α), uncoupling protein 1 (UCP-1), the second messenger cyclic guanosine-3', 5'-monophosphate (cGMP),PR domain containing 16 zinc finger transcription factor (Prdm16) and deiodinase, iodothyronine, type II (DIO2).The metabolic makers will be measured by blood pressure, heart rate, thyroid functions, resting metabolic rate, respiratory quotient, blood cGMP, blood insulin and blood glucose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sildenafil | Experimental | Drug: sildenafilEleven patients receive sildenafil 100mg/day (25 mg at 8 AM plus 25 mg at 4 PM plus 50 mg at 10 PM)for 7 days. |
| Placebo group | Placebo comparator | Drug: placeboAn identical placebo for 7 days in placebo group. |
Who may qualify
- Ages
- 20 to 30 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- overweight volunteers
- 20-30 years old
- body mass index >=25 kg/m2
- normal glucose tolerance
Key exclusion criteria (10 listed)
- normal body mass index
- abnormal cardiovascular status
- women
- history of any local or systemic infectious disease with fever or requiring antibiotic within four weeks of drug administration
- current addiction to alcohol or substances of abuse
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 |
|---|---|---|
| sildenafilsildenafil 100 mg per day for 7 days. | Drug | Sildenafil |
| placeboan identical placebo per day for 7 days | Drug | Placebo group |
Primary outcome
Browning of white adipose tissue
Time frame: 7 days
The browning of white adipose tissue was measured by Western blot (including the expressions of peroxisome proliferator-activated receptor-γ (PPARγ), PPARγcoactivator 1α (PGC-1α), uncoupling protein 1 (UCP-1), the second messenger cyclic guanosine-3', 5'-monophosphate (cGMP),PR domain containing 16 zinc finger transcription factor (Prdm16) and deiodinase, iodothyronine, type II (DIO2)).
1 secondary outcome
Improvement of insulin sensitivity
Time frame: 7days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2016.
- Derived from this study: PubMed 28986166Li S, Li Y, Xiang L, Dong J, Liu M, Xiang G. Sildenafil induces browning of subcutaneous white adipose tissue in overweight adults. Metabolism. 2018 Jan;78:106-117. doi: 10.1016/j.metabol.2017.09.008. Epub 2017 Oct 3.
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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.
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 sildenafil in people with Obesity, run by Xiang Guang-da at 1 site in China.
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 10 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: status not confirmed, as of the sponsor's last update on 2 Sep 2016. 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 China. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guangda Xiang, MD (086 027 50772191, Guangda64@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Browning of white adipose tissue (time frame: 7 days). 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 NCT02524184, 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 2 Sep 2016.