Trial Outcomes & Findings for Study of Serum Markers for Cardiovascular Risk in Obese Youth and Impact of Lifestyle and Medication Intervention (NCT NCT00139477)

Results Overview

Value at 6 months minus value at baseline. HsCRP is an acute phase protein which is a sensitive marker for systemic inflammation. HsCRP concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA), with an hsCRP lower sensitivity of 0.156 mg/L.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

66 participants

Primary outcome timeframe

Baseline and 6 months

Results posted on

2023-04-18

Participant Flow

Participants recruited from pediatric endocrinology clinics, in Jacksonville, USA between November 2003 and April 2008.

375 participants recruited; 177 obese participants screened, 111 excluded (62 did not meet inclusion criteria and 4 refused participation).

Participant milestones

Participant milestones
Measure	Diet/Exercise Only, Then Diet/Exercise Plus Metformin Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).	Diet/Exercise Plus Metformin, Then Diet/Exercise Only Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).
First Intervention -Baseline to 6Months STARTED	31	35
First Intervention -Baseline to 6Months COMPLETED	19	23
First Intervention -Baseline to 6Months NOT COMPLETED	12	12
Second Intervention -6Months to 12Months STARTED	19	23
Second Intervention -6Months to 12Months COMPLETED	14	18
Second Intervention -6Months to 12Months NOT COMPLETED	5	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Diet/Exercise Only, Then Diet/Exercise Plus Metformin Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).	Diet/Exercise Plus Metformin, Then Diet/Exercise Only Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).
First Intervention -Baseline to 6Months No Longer Interested	6	7
First Intervention -Baseline to 6Months Relocation	1	2
First Intervention -Baseline to 6Months Lost to Follow-up	3	3
First Intervention -Baseline to 6Months Impaired Glucose Tolerance at Screening	2	0
Second Intervention -6Months to 12Months No Longer Interested	0	2
Second Intervention -6Months to 12Months Relocation	1	0
Second Intervention -6Months to 12Months Lost to Follow-up	4	3

Baseline Characteristics

Study of Serum Markers for Cardiovascular Risk in Obese Youth and Impact of Lifestyle and Medication Intervention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Diet/Exercise Only, Then Diet/Exercise Plus Metformin n=31 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period).	Diet/Exercise Plus Metformin, Then Diet/Exercise Only n=35 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period).	Total n=66 Participants Total of all reporting groups
Age, Categorical <=18 years	31 Participants n=5 Participants	35 Participants n=7 Participants	66 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	12 years STANDARD_DEVIATION 0.4 • n=5 Participants	12.3 years STANDARD_DEVIATION 0.5 • n=7 Participants	12.2 years STANDARD_DEVIATION 2.7 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants	35 participants n=7 Participants	66 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: 1 Subject in the "Diet/Exercise plus Metformin, then Diet/Exercise (Pubertal)" Group did not have an hsCRP level available for analysis.

Value at 6 months minus value at baseline. HsCRP is an acute phase protein which is a sensitive marker for systemic inflammation. HsCRP concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA), with an hsCRP lower sensitivity of 0.156 mg/L.

Outcome measures

Outcome measures
Measure	Diet/Exercise, Then Diet/Exercise Plus Metformin (Prepubertal) n=8 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise, Then Diet/Exercise Plus Metformin (Pubertal) n=11 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise Plus Metformin, Then Diet/Exercise (Prepubertal) n=13 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise Plus Metformin, Then Diet/Exercise (Pubertal) n=9 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at 6 Months	-0.37 mg/dL Interval -1.54 to 0.81	-1.78 mg/dL Interval -5.49 to -0.15	-0.29 mg/dL Interval -1.42 to 1.79	0.00 mg/dL Interval -0.65 to 2.17

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: 1 Subject in the "Diet/Exercise plus Metformin, then Diet/Exercise (Pubertal)" Group did not have a Fibrinogen level available for analysis.

Value at 6 months minus value at baseline. Fibrinogen is a hepatic-derived factor directly involved in clotting and in the viscosity characteristics of blood flow. It binds to platelets and contributes to their aggregation, promotes fibrin formation and is also an acute phase reactant that is increased in inflammatory states. Fibrinogen concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA).

Outcome measures

Outcome measures
Measure	Diet/Exercise, Then Diet/Exercise Plus Metformin (Prepubertal) n=8 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise, Then Diet/Exercise Plus Metformin (Pubertal) n=11 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise Plus Metformin, Then Diet/Exercise (Prepubertal) n=13 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise Plus Metformin, Then Diet/Exercise (Pubertal) n=9 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.
Change From Baseline in Fibrinogen at 6 Months	58.5 mg/dL Interval -64.0 to 123.75	-105 mg/dL Interval -141.0 to -31.0	0.00 mg/dL Interval -51.5 to 83.0	-33 mg/dL Interval -93.5 to 40.5

PRIMARY outcome

Timeframe: Baseline and 6 months

Value at 6 months minus value at baseline. IL-6 is a pro-inflammatory cytokine thought to produce a state of low-grade inflammation in obese individuals. IL-6 stimulates hepatic production of C-reactive protein (CRP), an acute phase protein which is a sensitive marker for systemic inflammation. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA; R\&D Systems, Minneapolis, MN, USA).

Outcome measures

Outcome measures
Measure	Diet/Exercise, Then Diet/Exercise Plus Metformin (Prepubertal) n=8 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise, Then Diet/Exercise Plus Metformin (Pubertal) n=11 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise Plus Metformin, Then Diet/Exercise (Prepubertal) n=13 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise Plus Metformin, Then Diet/Exercise (Pubertal) n=10 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.
Change From Baseline in Interleukin 6 (IL-6) at 6 Months	-0.66 pg/mL Interval -2.39 to -0.01	-0.99 pg/mL Interval -2.11 to 0.22	0.2 pg/mL Interval -0.8 to 2.19	-0.35 pg/mL Interval -0.94 to 0.07

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: 1 Subject in the "Diet/Exercise plus Metformin, then Diet/Exercise (Pubertal)" Group and 1 Subject in the "Diet/Exercise, then Diet/Exercise plus Metformin (Pubertal)" Group did not have a PAI-1 level available for analysis.

Value at 6 months minus value at baseline. PAI-1 is the primary physiological inhibitor of fibrinolysis and proteolysis. High PAI-1 levels have been linked to thrombosis and fibrosis, insulin resistance and obesity. PAI-1 was measured by ELISA (American Diagnostica, Stamford, CT, USA).

Outcome measures

Outcome measures
Measure	Diet/Exercise, Then Diet/Exercise Plus Metformin (Prepubertal) n=8 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise, Then Diet/Exercise Plus Metformin (Pubertal) n=10 Participants Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise Plus Metformin, Then Diet/Exercise (Prepubertal) n=13 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.	Diet/Exercise Plus Metformin, Then Diet/Exercise (Pubertal) n=9 Participants Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants.
Change From Baseline in Plasminogen Activator Inhibitor-1 (PAI-1) at 6 Months	6.98 ng/ML Interval -48.54 to 14.4	-46.84 ng/ML Interval -62.86 to -24.46	0.55 ng/ML Interval -34.45 to 34.22	-34.42 ng/ML Interval -46.74 to 25.82

Adverse Events

Diet/Exercise Only, Then Diet/Exercise Plus Metformin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Diet/Exercise Plus Metformin, Then Diet/Exercise Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Nelly Mauras, Chief, Division of Endocrinology

Nemours Children's Clinic

Phone: 904-697-3674

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place