Trial Outcomes & Findings for Cardiometabolic Disease and Pulmonary Hypertension (NCT NCT03349775)

NCT ID: NCT03349775

Last Updated: 2022-01-21

Results Overview

The metformin and placebo groups will be compared with respect to resting mean pulmonary artery pressure (mmHg)

• Recruitment status: TERMINATED
• Study phase: EARLY_PHASE1
• Target enrollment: 21 participants
• Primary outcome timeframe: Baseline and 3 months
• Results posted on: 2022-01-21

Participant Flow

Participant milestones

Measure	Metformin Metformin: 500mg tablet orally twice daily for 1 week, followed by two 500mg tablets orally twice daily for a total of 3 months.	Placebo Placebo: 500 mg tablet orally twice daily for 1 week, followed by two 500 mg tablets orally twice daily for a total of 3 months.
Overall Study STARTED	10	11
Overall Study COMPLETED	8	7
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Measure	Metformin Metformin: 500mg tablet orally twice daily for 1 week, followed by two 500mg tablets orally twice daily for a total of 3 months.	Placebo Placebo: 500 mg tablet orally twice daily for 1 week, followed by two 500 mg tablets orally twice daily for a total of 3 months.
Overall Study Side Effects	1	2
Overall Study Withdrawal by Subject	1	1
Overall Study No primary outcome measurements	0	1

Baseline Characteristics

Cardiometabolic Disease and Pulmonary Hypertension

Baseline characteristics by cohort

Measure	Metformin n=8 Participants Metformin: 500mg tablet orally twice daily for 1 week, followed by two 500mg tablets orally twice daily for a total of 3 months.	Placebo n=7 Participants Placebo: 500 mg tablet orally twice daily for 1 week, followed by two 500 mg tablets orally twice daily for a total of 3 months.	Total n=15 Participants Total of all reporting groups
Age, Continuous	65 years STANDARD_DEVIATION 10 • n=93 Participants	60 years STANDARD_DEVIATION 10 • n=4 Participants	63 years STANDARD_DEVIATION 10 • n=27 Participants
Sex: Female, Male Female	5 Participants n=93 Participants	4 Participants n=4 Participants	9 Participants n=27 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=93 Participants	7 Participants n=4 Participants	15 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) White	7 Participants n=93 Participants	7 Participants n=4 Participants	14 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Height	65.1 inches STANDARD_DEVIATION 2.9 • n=93 Participants	67.7 inches STANDARD_DEVIATION 4.2 • n=4 Participants	66.3 inches STANDARD_DEVIATION 3.7 • n=27 Participants
Weight	212.9 pounds STANDARD_DEVIATION 44.1 • n=93 Participants	224.0 pounds STANDARD_DEVIATION 32.9 • n=4 Participants	218.1 pounds STANDARD_DEVIATION 38.3 • n=27 Participants
Body Mass Index (BMI)	35.3 kg/m^2 STANDARD_DEVIATION 6.0 • n=93 Participants	34.4 kg/m^2 STANDARD_DEVIATION 4.6 • n=4 Participants	34.9 kg/m^2 STANDARD_DEVIATION 5.2 • n=27 Participants
Heart Rate (HR)	70 beats per minute (bpm) STANDARD_DEVIATION 13 • n=93 Participants	70 beats per minute (bpm) STANDARD_DEVIATION 15 • n=4 Participants	70 beats per minute (bpm) STANDARD_DEVIATION 14 • n=27 Participants
Systolic Blood Pressure (SBP)	133 mmHg STANDARD_DEVIATION 18 • n=93 Participants	142 mmHg STANDARD_DEVIATION 14 • n=4 Participants	137 mmHg STANDARD_DEVIATION 17 • n=27 Participants
Diastolic Blood Pressure (DBP)	80 mmHg STANDARD_DEVIATION 8 • n=93 Participants	86 mmHg STANDARD_DEVIATION 11 • n=4 Participants	83 mmHg STANDARD_DEVIATION 9 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline and 3 months

The metformin and placebo groups will be compared with respect to resting mean pulmonary artery pressure (mmHg)

Outcome measures

Measure	Metformin n=8 Participants Metformin: 500mg tablet orally twice daily for 1 week, followed by two 500mg tablets orally twice daily for a total of 3 months.	Placebo n=7 Participants Placebo: 500 mg tablet orally twice daily for 1 week, followed by two 500 mg tablets orally twice daily for a total of 3 months.
Pulmonary Vascular Hemodynamics (Rest)	-3.00 mmHg Standard Deviation 5.35	-0.43 mmHg Standard Deviation 4.89

PRIMARY outcome

Timeframe: Baseline and 3 months

The metformin and placebo groups will be compared with respect to augmentation of mean pulmonary artery pressure divided by augmentation of cardiac output during cardiopulmonary exercise testing (change in mean PAP divided by change in cardiac output from rest to peak exercise)

Outcome measures

Measure	Metformin n=8 Participants Metformin: 500mg tablet orally twice daily for 1 week, followed by two 500mg tablets orally twice daily for a total of 3 months.	Placebo n=7 Participants Placebo: 500 mg tablet orally twice daily for 1 week, followed by two 500 mg tablets orally twice daily for a total of 3 months.
Pulmonary Vascular Hemodynamics (Exercise)	-0.29 mmHg/L/min Standard Deviation 0.83	-1.42 mmHg/L/min Standard Deviation 3.00

SECONDARY outcome

Timeframe: baseline and 3 months

We will compare the metformin and placebo groups. Specifically we will examine the following pulmonary artery endothelial cell phenotypes:

(1) activation of phospho-eNOS as detected by immunofluorescence staining

Outcome measures

Outcome data not reported

Adverse Events

Metformin

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Metformin n=10 participants at risk Metformin: 500mg tablet orally twice daily for 1 week, followed by two 500mg tablets orally twice daily for a total of 3 months.	Placebo n=11 participants at risk Placebo: 500 mg tablet orally twice daily for 1 week, followed by two 500 mg tablets orally twice daily for a total of 3 months.
Cardiac disorders Left arm numbness and chest pain	0.00% 0/10 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	9.1% 1/11 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.

Other adverse events

Measure	Metformin n=10 participants at risk Metformin: 500mg tablet orally twice daily for 1 week, followed by two 500mg tablets orally twice daily for a total of 3 months.	Placebo n=11 participants at risk Placebo: 500 mg tablet orally twice daily for 1 week, followed by two 500 mg tablets orally twice daily for a total of 3 months.
Respiratory, thoracic and mediastinal disorders Asthma Flare	0.00% 0/10 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	9.1% 1/11 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/10 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	9.1% 1/11 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.
Gastrointestinal disorders Acid Reflux	10.0% 1/10 • Number of events 2 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	0.00% 0/11 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.
Gastrointestinal disorders GI upset (e.g. nausea, diarrhea, vomiting, abdominal discomfort, flatulence)	70.0% 7/10 • Number of events 11 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	36.4% 4/11 • Number of events 5 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.
General disorders Fatigue/Weakness	0.00% 0/10 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	18.2% 2/11 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.
Skin and subcutaneous tissue disorders Itching and rash/hives	10.0% 1/10 • Number of events 2 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	9.1% 1/11 • Number of events 1 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.
Musculoskeletal and connective tissue disorders Muscle or joint soreness	0.00% 0/10 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	27.3% 3/11 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.
General disorders Non-Specific Symptoms	0.00% 0/10 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.	9.1% 1/11 • Adverse event data were collected for the metformin and placebo groups over the course of the 3 months on randomized assignment to study drug.

Additional Information

Dr. Jennifer Ho

Beth Israel Deaconness Medical Center

Phone: 617-735-4102

Email: jho@bidmc.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place