Trial Outcomes & Findings for Effects of Acipimox on Insulin Action, Vascular Function, and Muscle Function in Type 1 Diabetes (NCT NCT01816165)

NCT ID: NCT01816165

Last Updated: 2022-01-21

Results Overview

Evaluate the impact of Non esterified fatty acid (NEFA)-lowering on insulin sensitivity in T1D versus non-DM. Glucose infusion rate is reported normalized to lean body weight in kg and to final insulin concentration. The unit of measure reflects the rate at which glucose needs to be infused to maintain a normal blood sugar in the setting of a given serum insulin level from an insulin infusion. As such, a higher number means more glucose was needed and indicates greater sensitivity to insulin.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 28 participants
• Primary outcome timeframe: day 8 of each of the 2 random order intervention phases; max 16 weeks post enrollment
• Results posted on: 2022-01-21

Participant Flow

10 participants (7 withdrawals, 3 screen fails) were excluded from the study after enrollment, but prior to beginning the study. One T1D acipimox to placebo was withdrawn during the acipimox phase due to an SAE.

Participant milestones

Measure	Participants With T1 Diabetes: Acipimox, Then Placebo Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	Participants Without T1 Diabetes: Acipimox, Then Placebo Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	Participants With T1 Diabetes: Placebo, Then Acipimox Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	Participants Without T1 Diabetes: Placebo, Then Acipimox Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.
Overall Study STARTED	5	4	5	4
Overall Study Completed Intervention 1	4	4	5	4
Overall Study Completed ~2 Week Washout	4	4	5	4
Overall Study Started Second Intervention	4	4	5	4
Overall Study COMPLETED	4	4	5	4
Overall Study NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Measure	Participants With T1 Diabetes: Acipimox, Then Placebo Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	Participants Without T1 Diabetes: Acipimox, Then Placebo Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	Participants With T1 Diabetes: Placebo, Then Acipimox Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	Participants Without T1 Diabetes: Placebo, Then Acipimox Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.
Overall Study Adverse Event	1	0	0	0

Baseline Characteristics

Effects of Acipimox on Insulin Action, Vascular Function, and Muscle Function in Type 1 Diabetes

Baseline characteristics by cohort

Measure	All Participants With T1 Diabetes n=10 Participants Acipimox, Then Placebo: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day. Placebo, then Acipimox :Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	All Participants Without T1 Diabetes n=8 Participants Placebo, then Acipimox :Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day. Acipimox, Then Placebo: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day, followed by placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	8 Participants n=7 Participants	18 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	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	6 Participants n=7 Participants	16 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: day 8 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison.

Evaluate the impact of Non esterified fatty acid (NEFA)-lowering on insulin sensitivity in T1D versus non-DM. Glucose infusion rate is reported normalized to lean body weight in kg and to final insulin concentration.

The unit of measure reflects the rate at which glucose needs to be infused to maintain a normal blood sugar in the setting of a given serum insulin level from an insulin infusion. As such, a higher number means more glucose was needed and indicates greater sensitivity to insulin.

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Insulin Sensitivity: M-value From Hyperinsulinemic Euglycemia Clamp Study	4.65 mg/kg*minute*microIU/mL*100 Standard Deviation 1.52	3.67 mg/kg*minute*microIU/mL*100 Standard Deviation 1.45	8.8 mg/kg*minute*microIU/mL*100 Standard Deviation 3.04	9.05 mg/kg*minute*microIU/mL*100 Standard Deviation 2.88

PRIMARY outcome

Timeframe: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Assesses whether fatty acid level is consistently lowered by acipimox. Mean of fatty acid levels measured 22 times over 24 hours (hourly except 0100 and 0300 hours).

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
24 Hour Mean Fatty Acid Levels	343 microEq/L Standard Deviation 122	297 microEq/L Standard Deviation 56	298 microEq/L Standard Deviation 90	335 microEq/L Standard Deviation 65

PRIMARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison.

To determine the effects of NEFA lowering and insulin sensitization on endothelial function. Measures percent change in brachial artery diameter with hyperemia after occlusion.

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Percent Flow-mediated Brachial Artery Dilation	8.21 Percent change in BA diameter Standard Deviation 3.02	8.82 Percent change in BA diameter Standard Deviation 4.40	5.88 Percent change in BA diameter Standard Deviation 4.17	7.32 Percent change in BA diameter Standard Deviation 4.25

PRIMARY outcome

Timeframe: muscle biopsy on day 7 of each weeklong intervention period; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison. Another participant did not have a muscle biopsy collected (T1D, Acipimox).

Measures skeletal muscle mitochondrial function and effects of acipimox thereon, carbohydrate & lipid substrates. State 3 is fully active coupled oxygen flux using PMG or PMGS (pyruvate, malate, glutamate, +/- succinate) or OCMS (octanyl carnitine, malate, +/- succinate) as substrates. FCCP is added as an uncoupler to measure maximum possible O2 flux. Higher values reflect better mitochondrial function.

Outcome measures

Measure	T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
State 3 Mitochondrial Oxygen Consumption PMG State 3 Oxygen Flux	26.1 pmoles/mg/s Standard Deviation 8.3	24.9 pmoles/mg/s Standard Deviation 7.6	30.2 pmoles/mg/s Standard Deviation 9.8	29.7 pmoles/mg/s Standard Deviation 10.0
State 3 Mitochondrial Oxygen Consumption PMGS Uncoupled Max Oxygen Flux	65.2 pmoles/mg/s Standard Deviation 18.4	62.1 pmoles/mg/s Standard Deviation 16.3	77.8 pmoles/mg/s Standard Deviation 26.3	80.2 pmoles/mg/s Standard Deviation 28.9
State 3 Mitochondrial Oxygen Consumption OCM State 3 Oxygen Flux	14.0 pmoles/mg/s Standard Deviation 5.8	15.0 pmoles/mg/s Standard Deviation 5.6	18.8 pmoles/mg/s Standard Deviation 8.6	17.3 pmoles/mg/s Standard Deviation 4.4
State 3 Mitochondrial Oxygen Consumption OCMS State 3 Oxygen Flux	38.6 pmoles/mg/s Standard Deviation 14.6	38.5 pmoles/mg/s Standard Deviation 11.2	43.8 pmoles/mg/s Standard Deviation 13.3	41.7 pmoles/mg/s Standard Deviation 9.9
State 3 Mitochondrial Oxygen Consumption OCMS Uncoupled Max Oxygen Flux	51.8 pmoles/mg/s Standard Deviation 22.9	56.4 pmoles/mg/s Standard Deviation 20.0	80.1 pmoles/mg/s Standard Deviation 24.8	73.1 pmoles/mg/s Standard Deviation 18.8
State 3 Mitochondrial Oxygen Consumption PMGS State 3 Oxygen Flux	38.0 pmoles/mg/s Standard Deviation 11.8	36.9 pmoles/mg/s Standard Deviation 12.7	42.5 pmoles/mg/s Standard Deviation 15.0	42.5 pmoles/mg/s Standard Deviation 11.8

SECONDARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison.

Interleukin 6 (IL6)

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Oxidative Stress and Inflammatory Markers: Interleukin 6 (IL6)	2.8 picograms/mL Standard Deviation 1.6	4.2 picograms/mL Standard Deviation 3.2	2.6 picograms/mL Standard Deviation 2.4	3.5 picograms/mL Standard Deviation 1.3

SECONDARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison. Two other participants (T1D, Acipimox; No T1D Acipimox) did not have data collected.

TNFalpha

Outcome measures

Measure	T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=7 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Oxidative Stress and Inflammatory Markers: TNFalpha	1.76 picograms/mL Standard Deviation 1.08	1.71 picograms/mL Standard Deviation .80	1.56 picograms/mL Standard Deviation .95	.91 picograms/mL Standard Deviation .46

SECONDARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison. Another participant from the Non T1D Placebo group did not have data collected.

high-sensitivity C-reactive protein (hsCRP)

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=7 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Oxidative Stress and Inflammatory Markers: High-sensitivity C-reactive Protein (hsCRP)	3.19 mg/L Standard Deviation 3.84	1.98 mg/L Standard Deviation 1.64	1.43 mg/L Standard Deviation 1.11	1.44 mg/L Standard Deviation 1.42

SECONDARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison. Two participants (one in each of the Non-T1D study phases) did not have data collected.

adiponectin

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=7 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=7 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Oxidative Stress and Inflammatory Markers: Adiponectin	11.6 micrograms/mL Standard Deviation 7.7	14.9 micrograms/mL Standard Deviation 10.8	7.3 micrograms/mL Standard Deviation 5.0	5.8 micrograms/mL Standard Deviation 2.1

SECONDARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: Measure was not collected due to funding limitations.

Plasminogen activator inhibitor (PAI-1)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison.

Measure of autonomic function; ratio of fastest to slowest heart rate during valsalva maneuver.

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Heart Rate Variability	1.37 ratio Standard Deviation .17	1.43 ratio Standard Deviation .14	1.59 ratio Standard Deviation .19	1.69 ratio Standard Deviation .30

SECONDARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison. Additionally, one participant in each of the T1D study phases did not have data collected.

Pulse wave velocity by Sphygmacor as a measure of aortic stiffness in m/sec. Higher values reflect a stiffer vasculature.

Outcome measures

Measure	T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Arterial Stiffness (PWV)	9.24 m/sec Standard Deviation 2.46	9.91 m/sec Standard Deviation 3.30	6.97 m/sec Standard Deviation 1.71	7.4 m/sec Standard Deviation 1.00

SECONDARY outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison. Additionally, one participant in each of the T1D study phases did not have data collected.

Augmentation index by Sphygmacor is a measure of aortic arterial stiffness. AI@75 is the ratio of augmented pressure/pulse pressure adjusted to a heart rate of 75.

Higher values indicate stiffer vessels

Outcome measures

Measure	T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Arterial Stiffness (AI)	21.4 ratio Standard Deviation 8.4	19.7 ratio Standard Deviation 10.0	11.1 ratio Standard Deviation 13.0	12.4 ratio Standard Deviation 12.7

SECONDARY outcome

Timeframe: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison.

Continuous glucose monitoring measures for 3 days before clamp. Collected for participants with T1 Diabetes only.

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Metabolic Markers: Continuous Glucose Monitoring Measures Average Glucose	8.82 mmol/L Standard Deviation 1.2	9.09 mmol/L Standard Deviation 0.72	—	—
Metabolic Markers: Continuous Glucose Monitoring Measures Glycemic Variability	3.64 mmol/L Standard Deviation 0.92	3.64 mmol/L Standard Deviation 0.66	—	—

SECONDARY outcome

Timeframe: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

mean glucose and triglycerides for the 24 hours before the 2nd overnight stay from 22 hourly measurements over 24 hours (except 0100 and 0300).

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Metabolic Markers: Mean 24 Hour Triglyceride and Glucose Levels glucose	135 mg/dL Standard Deviation 28	131 mg/dL Standard Deviation 31	87 mg/dL Standard Deviation 10	89 mg/dL Standard Deviation 8
Metabolic Markers: Mean 24 Hour Triglyceride and Glucose Levels triglycerides	59 mg/dL Standard Deviation 29	68 mg/dL Standard Deviation 33	67 mg/dL Standard Deviation 20	83 mg/dL Standard Deviation 27

SECONDARY outcome

Timeframe: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

mean insulin for the 24 hours before the 2nd overnight stay from 22 hourly measurements over 24 hours (except 0100 and 0300).

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Metabolic Markers: Insulin	48 microIU/mL Standard Deviation 25	47 microIU/mL Standard Deviation 26	20 microIU/mL Standard Deviation 6	21 microIU/mL Standard Deviation 10

SECONDARY outcome

Timeframe: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

mean glycerol for the 24 hours before the 2nd overnight stay from 22 hourly measurements over 24 hours (except 0100 and 0300).

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=8 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Metabolic Markers: Glycerol	86 micromoles/L Standard Deviation 25	75 micromoles/L Standard Deviation 20	63 micromoles/L Standard Deviation 12	69 micromoles/L Standard Deviation 14

SECONDARY outcome

Timeframe: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison. in addition, the last nonDM subjects did not have this collected due to funding limitations and futility based on prior results.

endothelin 1 measured as a marker of vascular damage

Outcome measures

Measure	T1 Diabetes, Acipimox n=9 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Diabetes, Placebo n=9 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=6 Participants Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Diabetes, Placebo n=6 Participants Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Vascular Markers	4.92 pg/mL Standard Deviation 1.56	4.9 pg/mL Standard Deviation 0.91	4.83 pg/mL Standard Deviation 0.92	4.12 pg/mL Standard Deviation 1.00

OTHER_PRE_SPECIFIED outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: Originally described as secondary but were actually exploratory. Not done due to funding and tissue limitations.

Mito content and electron transport chain complexes by western blot analysis.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: These oxidative stress and inflammatory markers were collected, but assays were found to be unreliable. These measurements were originally erroneously described as secondary outcome measures, but are exploratory.

thiobarbituric acid reactive substances (TBARs), glutathione disulfide (GSSG): reduced Glutathione (GSH) ratio; amplex red assay of hydrogen peroxide (H2O2) production,

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: day 6 to 7 of each of the 2 random order intervention phases; max 16 weeks post enrollment

Population: 1 participant in the T1 Diabetes groups was excluded from the analysis because data was only collected in the Acipimox phase and matching Placebo data would have been required for comparison. Incorrectly listed as secondary outcome. This was an exploratory outcome.

Planned glucagon and cortisol as a markers of counteregulation, but not done due to financial limitations

Outcome measures

Outcome data not reported

Adverse Events

T1 Diabetes, Acipimox

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

T1 Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

No T1 Diabetes, Acipimox

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

No T1 Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	T1 Diabetes, Acipimox n=10 participants at risk Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	T1 Placebo n=9 participants at risk Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day	No T1 Diabetes, Acipimox n=8 participants at risk Drug: acipimox Acipimox: Subjects will take acipimox 250mg by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day.	No T1 Placebo n=8 participants at risk Drug: Placebo Placebo: Subjects will take placebo by mouth four times a day for a total of seven days plus one dose the morning of the final study visit day
Cardiac disorders bradycardia	10.0% 1/10 • Number of events 1 • Up to about Week 16	0.00% 0/9 • Up to about Week 16	0.00% 0/8 • Up to about Week 16	0.00% 0/8 • Up to about Week 16

Other adverse events

Adverse event data not reported

Additional Information

Irene Schauer, MD

University of Colorado Denver

Phone: 3037241111

Email: clinicaresearchsupportcenter@ucdenver.edu

Results disclosure agreements

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