Intra-Arterial Microdosing: Proof-of-Concept in Humans

NCT02304211 | Completed Early Phase 1

• 1 other identifier: Pro00056933
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this protocol is to demonstrate that intra-arterial administration of a drug can generate information in a manner that faithfully mimics effects of systemic administration but with little or no systemic effects.

Conditions

Healthy

Keywords

Microdosing; Phase 0; Exploratory Investigational New Drug (IND); Intra-Arterial; PET Imaging

Outcome Measures

Primary Outcomes (2)

• Glucose Plasma Levels

  2 hours

• 18F-FDG Uptake as measured with Positron Emission Tomography (PET) imaging

  2 hours

Secondary Outcomes (2)

• Potassium Plasma Levels

  2 hours

• Lactic Acid Plasma Levels

  2 hours

Study Arms (2)

Intra-Arterial Microdose Insulin

EXPERIMENTAL

Healthy volunteers will receive microdose insulin intra-arterially into the radial artery.

Drug: Insulin

Systemic Insulin

ACTIVE COMPARATOR

Healthy volunteers will receive full-dose insulin intra-venously.

Drug: Insulin

Interventions

Insulin DRUG

Insulin will be administered either into the radial artery (microdose intervention) or IV (systemic intervention).

Intra-Arterial Microdose Insulin; Systemic Insulin

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Healthy, non-smoking male subjects, 18 - 40 years of age with a BMI of 18 - 32 kg/m2 \[BMI is rounded to the nearest tenth - a BMI of 32.045 should be rounded up to 32.05, which also would be rounded up to 32.1 and subject would be excluded; a BMI of 32.044 should be rounded down to 32.04 which would also be rounded down to 32.0 and the subject would be included\].
• Subject's health status will be determined by the medical history, physical examination, vital signs, electrocardiogram, blood chemistry, hematology, and urinalysis performed at screening.
• Subjects must be willing to fast a minimum of 8 hours.
• Subjects must be willing to abstain from alcohol from 2 days prior to Day 1 of the study until discharge.
• Subjects must be willing to remain in the clinical research unit for the inpatient portion of the study from admission to discharge on Day 1.
• Subjects must agree not to donate blood, plasma, platelets, or any other blood components during the study and for 4 weeks after completion of the study.
• Renal function (creatinine clearance \[CLcr\] \> 80 mL/min as calculated using the Cockcroft-Gault equation using lean body weight \[LBW\]) (Cockcroft and Gault 1976)
• Subjects must have adequate arterial and venous access for receiving intra-arterial insulin infusions and placement of intravenous catheters for the collection of biomarker samples; and a positive Allen Test.

You may not qualify if:

• Subjects with laboratory results outside the normal range, if considered clinically significant by the Investigator.
• Hemoglobin concentration \< 12.0 g/dL.
• A mental capacity that is limited to the extent that the subject cannot provide legal consent or understand information regarding the potential risks of the study procedures and potential side effects of the investigational product.
• Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years.
• Unwillingness or lack of ability to comply with the protocol or cooperate fully with the Principal Investigator and site personnel.
• Use of any of the following:
• Any concomitant medication. Subjects who have received any prescribed or non-prescribed (over-the-counter \[OTC\]) systemic, topical, or oral medications, herbal or vitamin supplements within 14 days from Day 1. St. John's Wort (hypericin) must not have been taken for at least 30 days prior Day 1.
• Any drugs, foods or substances known to interfere with the acute effects of insulin or the biomarkers being evaluated within 14 days prior to Day 1.
• Caffeine-or xanthine-containing products for 24 hours prior to Day 1 until discharged.
• Use of alcohol for 48 hours prior to Day 1 until discharged.
• Clinically significant ECG abnormality in the opinion of the Investigator.
• Vital signs or clinically significant laboratory values at the screening visit that in the opinion of the Investigator would make the subject an inappropriate candidate for the study.
• Has taken any investigational drug during the previous 30 days (or 5 half-lives, whichever is longer) prior to the screening visit or is currently participating in another investigational clinical trial.
• Made any significant (as assessed by the investigator) donation (including plasma) or have had a significant loss of blood within 90 days prior to Day 1.
• History or manifestation of clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, pulmonary, metabolic, endocrine, hematologic or other medical disorders.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Burt T, Rouse DC, Lee K, Wu H, Layton AT, Hawk TC, Weitzel DH, Chin BB, Cohen-Wolkowiez M, Chow SC, Noveck RJ. Intraarterial Microdosing: A Novel Drug Development Approach, Proof-of-Concept PET Study in Rats. J Nucl Med. 2015 Nov;56(11):1793-9. doi: 10.2967/jnumed.115.160986. Epub 2015 Aug 27.

  PMID: 26315828 BACKGROUND

MeSH Terms

Interventions

Insulin

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Robert J. Noveck, M.D., Ph.D.

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2014
• First Posted: December 1, 2014
• Study Start: December 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: December 23, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)