Sildenafil Activates Browning of White Adipose and Improves Insulin Sensitivity

NCT02524184 | Unknown Phase 4 DMC

• 1 other identifier: Wze20150088
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Obesity

Outcome Measures

Primary Outcomes (1)

• 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)).

  7 days

Secondary Outcomes (1)

• Improvement of insulin sensitivity

  7days

Other Outcomes (1)

• Change of metabolic status

  3 months

Study Arms (2)

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.

Drug: sildenafil

Placebo group

PLACEBO COMPARATOR

An identical placebo for 7 days in placebo group.

Drug: placebo

Interventions

sildenafil DRUG

sildenafil 100 mg per day for 7 days.

Sildenafil

placebo DRUG

an identical placebo per day for 7 days

Placebo group

Eligibility Criteria

• Age: 20 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• overweight volunteers
• years old
• body mass index \>=25 kg/m2
• normal glucose tolerance

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Xiang Guang-da: lead

Study Sites (1)

Wuhan General Hospital

Wuhan, Hubei, 430070, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 28986166 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Guangda Xiang, MD

CONTACT

086 027 50772191; Guangda64@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Endocrinol Dept.

Study Record Dates

• First Submitted: August 2, 2015
• First Posted: August 14, 2015
• Study Start: August 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 2, 2016

Record last verified: 2016-08

Locations

CN (1)