The NICE-PAD II Trial

ConditionPeripheral Artery Disease (PAD)

Trial statusNot yet recruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age50+

SponsorNorthwestern University

About this trial

Among people with peripheral artery disease (PAD) age 50 and older, the investigators will test the hypothesis that PAD participants randomized to nicotinamide riboside (NR) will have greater improvement or less decline in six-minute walk distance at six-month follow-up, compared to those randomized to placebo. The study will randomize 250 participants with PAD age 50 and older to one of two groups for six months: nicotinamide riboside vs placebo. Our primary outcome is change in six-minute walk distance at six-month follow-up. Secondary outcomes are Walking Impairment Questionnaire (WIQ) distance score, PROMIS Mobility score, calf muscle perfusion (measured by magnetic resonance arterial spin labeling (MRI ASL)), oxidative stress (measured by plasma oxidized LDL), NAD+ abundance in whole blood, 6-minute walk improvement by baseline whole blood NAD+ levels, and 6-minute walk distance at 4 weeks after intervention completion.

To achieve the specific aims, the study will randomize 250 participants age 50 and older with PAD to one of two groups: nicotinamide riboside vs placebo. Participants will be followed for six months, with an additional four-week follow-up period after completion of the study intervention.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

1. Age 50 and older.

2. Presence of peripheral artery disease (PAD). PAD will be defined as either: a. An ABI < 0.90 at baseline. b. Vascular lab evidence of PAD (such as a toe brachial pressure < 0.70 or an ankle brachial index less than or equal to 0.90), or angiographic evidence of PAD defined as at least 70% stenosis of an artery supplying the lower extremities. c. An ABI of >0.90 and <1.00 who experience a 20% or greater drop in ABI in either leg after the heel-rise test.

Disqualifiers

1. Above- or below-knee amputation

2. Critical limb ischemia defined as an ABI <0.40 with symptoms of rest pain

3. Wheelchair confinement or requiring a walker to ambulate

4. Walking is limited by a symptom other than PAD

Trial design

Design model

Parallel

Treatments tested in this trial

Nicotinamide Riboside (NR)
Drug
The nicotinamide riboside intervention is manufactured by ChromaDex. Participants randomized to nicotinamide riboside will take two capsules twice daily. Each capsule contains 250 mg of nicotinamide riboside, for a total of 1000 mg of nicotinamide riboside per day.
Placebo
Drug
The placebo is manufactured by ChromaDex and is visually identical to the nicotinamide riboside capsules. Participants randomized to placebo will take two capsules twice daily. The placebo will not contain any nicotinamide riboside.

Treatment groups

250 Participants

are divided into 2 treatment groups

Group A: Nicotinamide riboside (NR)Active comparator 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

Six-minute walk distance

Change in six-minute walk distance between baseline and 6-month follow-up.

Time frame

Baseline to 6-months

Secondary outcomes

Walking Impairment Questionnaire (WIQ) distance score

Patient reported outcome measuring assessing participant perceived ability to walk distances. Scored on a 0-100 scale, 100-best.

Time frame

Baseline to 6-month follow-up

PROMIS Mobility score.

Patient reported outcome measure of mobility.

Time frame

Baseline to 6-month follow-up

Calf muscle perfusion

Calf muscle perfusion measured by magnetic resonance imaging (MRI) arterial spin labeling.

Time frame

Baseline to 6-month follow-up

Oxidative stress

Measured by plasma oxidized LDL.

Time frame

Baseline to 6-month follow-up

Other outcomes

Mitochondrial activity in gastrocnemius muscle

Mitochondrial oxygen consumption measured by respirometry using the Oroborus.

Time frame

Baseline to 6-month follow-up

Gastrocnemius muscle NAD+ abundance

NAD+ abundance measured in gastrocnemius muscle

Time frame

Baseline to 6-month follow-up

Gastrocnemius muscle sirtuin1 (SIRT1)

Gastrocnemius muscle biopsy measure of sirtuin1 (SIRT1).

Time frame

Baseline to 6-month follow-up

Gastrocnemius muscle phosphorylated endothelial nitric oxide synthase (eNOS)

Ratio of phosphorylated endothelial nitric oxide synthase (eNOS) to total eNOS in gastrocnemius muscle biopsies

Time frame

Baseline to 6-month follow-up

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Northwestern University

Lead sponsor

National Institute on Aging (NIA)

Collaborator

University of Chicago

Collaborator

University of Minnesota

Collaborator

Source ClinicalTrials.gov

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