Trial Outcomes & Findings for Beige Fat, Energy, and the Natriuretic Peptide System (NCT NCT04357964)

Last Updated: 2024-08-01

Results Overview

Primary endpoint is adipose tissue gene expression of UCP1 (Uncoupling Protein 1)- differences by obesity status (obese vs. lean). Units for primary endpoint are relative UCP1 gene expression (quantified using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR)), normalized to a housekeeping gene.

Recruitment status

COMPLETED

Target enrollment

137 participants

Primary outcome timeframe

Study Day 1

Results posted on

2024-08-01

Participant Flow

Enrolled subjects underwent a screening visit to determine eligibility for the study. The screening visit included a medical history, physical examination, calculation of BMI, and a blood draw for CMP, CBC, HbA1c, TSH, and free T4. A pregnancy test was completed on female subjects of child-bearing potential. Eligible subjects who still wished to participate in the study were then enrolled for the main study visit.

Participant milestones

Participant milestones
Measure	Lean Individuals Body Mass Index (BMI) ≥18.5 and \<25 kg/m2 (As defined per protocol)	Obese Individuals BMI ≥30 kg/m2 (as defined by protocol)
Overall Study STARTED	55	82
Overall Study COMPLETED	37	81
Overall Study NOT COMPLETED	18	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Lean Individuals Body Mass Index (BMI) ≥18.5 and \<25 kg/m2 (As defined per protocol)	Obese Individuals BMI ≥30 kg/m2 (as defined by protocol)
Overall Study Deemed not to have enough sufficient adipose tissue to undergo subcutaneous adipose biopsy	5	0
Overall Study Did not have usable primary endpoint data due to insufficient or low-quality adipose sample	13	0
Overall Study Adipose sample was insufficient quality	0	1

Baseline Characteristics

Beige Fat, Energy, and the Natriuretic Peptide System

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lean Individuals n=37 Participants lean individuals (BMI \>= 18.5 and \<25 kg/m2)	Obese Individuals n=81 Participants obese individuals (BMI\>= 30 kg/m2)	Total n=118 Participants Total of all reporting groups
Age, Continuous	39 years n=5 Participants	52 years n=7 Participants	47 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	50 Participants n=7 Participants	61 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	31 Participants n=7 Participants	57 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	14 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	64 Participants n=7 Participants	95 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	37 Participants n=5 Participants	81 Participants n=7 Participants	118 Participants n=5 Participants

PRIMARY outcome

Timeframe: Study Day 1

Population: All participants who had data for primary endpoint (adipose tissue UCP1 gene expression).

Outcome measures

Outcome measures
Measure	Lean Individuals n=37 Participants lean individuals (BMI between 18.5 and 24.9 kg/m2)	Obese Individuals n=81 Participants obese individuals (BMI\>= 30 kg/m2)
Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Obesity Status	7.79 fold change Interval 3.26 to 16.33	24.33 fold change Interval 16.5 to 40.93

SECONDARY outcome

Timeframe: Study Day 1

Population: Correlation between UCP1 gene expression and natriuretic peptide receptor-C (NPR-C) gene expression. The groups are combined in this analysis because the investigators had pre-specified that this secondary outcome would analyze this correlation across all individuals (lean and obese combined) for whom gene expression data was available.

The investigators will determine associations of adipose tissue gene expression of UCP1 with natriuretic peptide markers (natriuretic peptide receptor gene expression in adipose tissue, and circulating natriuretic peptide levels)

Outcome measures

Outcome measures
Measure	Lean Individuals n=118 Participants lean individuals (BMI between 18.5 and 24.9 kg/m2)	Obese Individuals obese individuals (BMI\>= 30 kg/m2)
Associations of Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1) With Natriuretic Peptide Markers	0.28 correlation coefficient	—

SECONDARY outcome

Timeframe: Study Day 1

Population: All participants who had data for primary endpoint (adipose tissue UCP1 gene expression), and who also self-reported their race as "white" or "black".

The investigators will determine adipose tissue gene expression of UCP1 (Uncoupling Protein 1), and analyze differences by race (blacks compared with whites).

Outcome measures

Outcome measures
Measure	Lean Individuals n=19 Participants lean individuals (BMI between 18.5 and 24.9 kg/m2)	Obese Individuals n=96 Participants obese individuals (BMI\>= 30 kg/m2)
Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Race	14.7 fold change Interval 11.2 to 28.5	20.9 fold change Interval 10.0 to 37.3

Adverse Events

Lean Individuals

Serious events: 0 serious events

Other events: 8 other events

Deaths: 8 deaths

Obese Individuals

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lean Individuals n=55 participants at risk BMI ≥18.5 and \<25 kg/m2 (as defined by protocol)	Obese Individuals n=22 participants at risk BMI ≥30 kg/m2 (as defined by protocol) A total of 22 obese individuals underwent procedures in the current study and thus there were 22 obese individuals "at risk" for an adverse event in the present study. Separately, we analyzed the samples/data from 60 obese individuals from a previously conducted study, but these subjects were not "at risk" for an adverse event in the present study since they did not undergo procedures in the present study.
Skin and subcutaneous tissue disorders Local skin reaction	7.3% 4/55 • Number of events 4 • Approximately 1 year A total of 22 obese individuals underwent procedures in the current study and thus there were 22 obese individuals "at risk" for an AE in the present study. Separately, we analyzed the baseline samples/data from 60 obese individuals from a previously conducted study, but these subjects were not "at risk" for an adverse event in the present study since they did not undergo procedures in the present study. AE's from this previous study are listed at: https://clinicaltrials.gov/study/NCT03101930.	0.00% 0/22 • Approximately 1 year A total of 22 obese individuals underwent procedures in the current study and thus there were 22 obese individuals "at risk" for an AE in the present study. Separately, we analyzed the baseline samples/data from 60 obese individuals from a previously conducted study, but these subjects were not "at risk" for an adverse event in the present study since they did not undergo procedures in the present study. AE's from this previous study are listed at: https://clinicaltrials.gov/study/NCT03101930.
Gastrointestinal disorders Nausea	3.6% 2/55 • Number of events 2 • Approximately 1 year A total of 22 obese individuals underwent procedures in the current study and thus there were 22 obese individuals "at risk" for an AE in the present study. Separately, we analyzed the baseline samples/data from 60 obese individuals from a previously conducted study, but these subjects were not "at risk" for an adverse event in the present study since they did not undergo procedures in the present study. AE's from this previous study are listed at: https://clinicaltrials.gov/study/NCT03101930.	0.00% 0/22 • Approximately 1 year A total of 22 obese individuals underwent procedures in the current study and thus there were 22 obese individuals "at risk" for an AE in the present study. Separately, we analyzed the baseline samples/data from 60 obese individuals from a previously conducted study, but these subjects were not "at risk" for an adverse event in the present study since they did not undergo procedures in the present study. AE's from this previous study are listed at: https://clinicaltrials.gov/study/NCT03101930.
Vascular disorders Lightheaded	5.5% 3/55 • Number of events 3 • Approximately 1 year A total of 22 obese individuals underwent procedures in the current study and thus there were 22 obese individuals "at risk" for an AE in the present study. Separately, we analyzed the baseline samples/data from 60 obese individuals from a previously conducted study, but these subjects were not "at risk" for an adverse event in the present study since they did not undergo procedures in the present study. AE's from this previous study are listed at: https://clinicaltrials.gov/study/NCT03101930.	0.00% 0/22 • Approximately 1 year A total of 22 obese individuals underwent procedures in the current study and thus there were 22 obese individuals "at risk" for an AE in the present study. Separately, we analyzed the baseline samples/data from 60 obese individuals from a previously conducted study, but these subjects were not "at risk" for an adverse event in the present study since they did not undergo procedures in the present study. AE's from this previous study are listed at: https://clinicaltrials.gov/study/NCT03101930.

Additional Information

Alp Ikizler, Catherine McLaughlin Hakim Chair in Vascular Biology, Professor of Medicine

Vanderbilt University Medical Center

Phone: (615) 343-7592

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place