Model System for Transient Forearm Blood Vessel Dysfunction

NCT00453531 | Completed Phase 1 FDA Drug

• 2 other identifiers: 07012407-H-0124
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study will develop a model system that can be used to test medications for improving the ability of blood vessels to resist damage from diseases such as heart attack and stroke. The endothelium (inner layer of blood vessels) has built-in defense mechanisms to prevent blockage of blood flow, including the ability to stretch the vessel when it senses that blood flow is threatened. People with heart attack risk factors, such as high cholesterol, smoking and diabetes lose this ability. This study will develop a model that can measure the response to a lack of blood flow in the arm and be used to test new medicines to improve blood vessel health. Healthy males between 18 and 45 years of age who have no history of high blood pressure, high cholesterol, or diabetes and who have not smoked for at least 3 months before entering the study may be eligible to enroll. Participants lie in an adjustable reclining bed. Small catheters (tubes) are placed in the artery and vein of the forearm of the non-dominant arm at the inside of the elbow. Blood samples are collected from the tubes. Then, pressure cuffs are placed on both wrists and upper arms. A strain gauge (rubber band-type device) is placed around the forearms. The pressure cuffs are inflated and blood flows into the forearm, stretching the strain gauge at a rate proportional to the blood flow. Then, small doses of acetylcholine (a medicine that causes blood vessels to expand) are injected into the artery tube. After 20 minutes, blood flow to the non-dominant arm is blocked by inflating the pressure cuff. The subject squeezes a rubber ball about every 2 seconds for 90 seconds. The cuff is deflated after 15 minutes and blood samples are withdrawn from the tube in the vein. After 15 minutes, the procedure is repeated one more time.

Conditions

Limb Ischemia; Ischemic Preconditioning

Keywords

Forearm Ischemia; Endothelial Function; Acetyicholine Vasodilation; Venous Plethysmography; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Change in vascular endothelial function.

Secondary Outcomes (1)

• Assessment of systemic effects of this model system by assess contralateral arm blood flow and by assessing metabolic response to the combined exercise/ischemic stress.

Study Arms (1)

Healthy Volunteers

EXPERIMENTAL

Procedure: Limb Ischemia; Drug: Acetylcholine

Interventions

Limb Ischemia PROCEDURE

Healthy Volunteers

Acetylcholine DRUG

Healthy Volunteers

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be 18-45 years of age.
• Subjects must be male.
• Subject must be in good health.
• Subject must complete a screening history and physical exam.
• Subjects must provide informed, written consent for participation in this study.

You may not qualify if:

• Subjects with a history of cardiac, pulmonary, peripheral vascular disease, coagulopathy, or any other disease predisposing to vasculitis or Raynaud's phenomenon.
• Subjects with diabetes or mitochondrial disease.
• Subjects with a history or evidence of present or past hypertension (blood pressure greater than 140/90 mmHg), hypercholesterolemia (LDL cholesterol greater than 160 mg/dL).
• Subjects with abnormal EKG other than sinus bradycardia.
• Subjects who have a history of smoking within three months.
• Subjects with anemia (defined as hemoglobin less than 9 g/dL).
• BMI greater than 30
• No volunteer subject will be allowed to take any prescription medication. Vitamin supplements, herbal preparations, nutraceuticals or other alternative therapies must be stopped for two weeks prior to study and aspirin, tylenol and NSAIDs must also be discontinued two weeks prior to study.
• Subjects with a blood pressure of less than 90/60 mmHg or mean arterial pressure (MAP) less than 70 mmHg on the study day will be excluded from the protocol.
• Positive for HIV or Hepatitis B, C.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27.

  PMID: 15623546 BACKGROUND

• Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30. doi: 10.1161/01.cir.103.12.1624.

  PMID: 11273988 BACKGROUND

• Broadhead MW, Kharbanda RK, Peters MJ, MacAllister RJ. KATP channel activation induces ischemic preconditioning of the endothelium in humans in vivo. Circulation. 2004 Oct 12;110(15):2077-82. doi: 10.1161/01.CIR.0000144304.91010.F0. Epub 2004 Oct 4.

  PMID: 15466634 BACKGROUND

MeSH Terms

Interventions

Acetylcholine

Intervention Hierarchy (Ancestors)

Biogenic Amines; Amines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 28, 2007
• First Posted: March 29, 2007
• Study Start: March 26, 2007
• Primary Completion: February 11, 2009
• Study Completion: February 11, 2009
• Last Updated: August 9, 2022

Record last verified: 2009-02

Locations

US (1)