Exercise-induced Ischemia and the Influence of Pain Modulation in a Nerve Growth Factor (NGF) Model

Interaction Between NGF and Exercise-induced Ischemia, and the Influence of the Pain Modulating System in a Prolonged NGF Sensitized Muscle.

The purpose of this study is to investigate responses of pain and the maintenance of mechanical muscle hypersensitivity following an acute exercise-induced ischemic condition repeated over time in a prolonged NGF-sensitized muscle. Additionally, the influence of the pain modulating system on prolonged NGF muscle hypersensitivity caused by peripheral mechanisms and central mechanisms will also be investigated.

Study Overview

• Status: Unknown
• Conditions: Healthy Subjects; Hyperalgesia; Pain Response
• Intervention / Treatment: Drug: NGF; Drug: Isotonic-saline

Detailed Description

The hypothesis is that an ischemic conditioning in a NGF-sensitized muscle is able to facilitate pain responses and that over time the pain modulation system is responsible for a subsequent reduction in muscle sensitivity towards mechanical pressure and a decrease in pain intensity following a period of NGF-induced muscle hypersensitivity.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Line Bay Sørensen, PhD. stud.; Phone Number: 52373229; Email: lbs@hst.aau.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9220
    • Recruiting
    • Aalborg University
    • Contact: Line Bay Sørensen, Ph.d stud.; Phone Number: 99404874; Email: lbs@hst.aau.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy and pain free volunteers

Exclusion Criteria:

• Pregnancy
• Drug addiction defined as the use of cannabis, opioids or other drugs
• Previous neurologic, mental illnesses, or psychiatric diseases.
• Past history of chronic pain in the musculoskeletal system (muscle, joint, cartilage, connective tissue)
• Participation in other pain trials throughout the study period
• Lack of ability to cooperate
• Taking any analgesic 24 hours before the injections
• Performing any strenuous leg exercise through out the study period causing sore muscles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NGF condition + Control condition; All participants will receive 3 single injection of NGF (1ug/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. After 4 weeks: All participants will receive 3 single injection of isotonic-saline (9%/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle.	Drug: NGF; Intramuscular injection; Other Names: Beta-Nerve Growth Factor, Human; Drug: Isotonic-saline; Intramuscular injection; Other Names: Control
Experimental: Control condition + NGF condition; All participants will receive 3 single injection of isotonic-saline (9%/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. After 4 weeks: All participants will receive 3 single injection of NGF (1ug/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle.	Drug: NGF; Intramuscular injection; Other Names: Beta-Nerve Growth Factor, Human; Drug: Isotonic-saline; Intramuscular injection; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle pain sensitivity (PPTs values) assessed by pressure algometer	Pressure pain thresholds (PPTs) are assessed over the dominant tibialis anterior muscle using a handhold pressure algometer.	Change from baseline at 3 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ischemic-induced pain intensity	Subjects perform a repeated static exercise with their dominant leg while a cuff is mounted over the knee to occlude the blodflow from the muscle (ischemia). Subjects subsequently rate their perceived pain intensity verbally on a 11-point numeric rating scale (NRS) rating from 0 (no pain) to 10 (worst pain imaginable).	Assessed right after the exercise has been performed, change from baseline at 3 weeks
Functional muscle pain	Subjects evaluate their muscle pain during movement using a 7-point Likert Scale for lower limp rating from 0 (a complete absence of pain) to 6 (a severe pain that limits my ability to move).	Change from baseline at 3 weeks
Conditioning pain modulation (CPM) efficacy	A test stimuli will be applied and compared with a test stimuli simultaneous a condition stimuli.	Change from baseline at 3 weeks
Temporal summation of pain	10 repeated stimuli will be applied and subjects will be asked to rate the pain for each individual stimuli on a 11-point visual analogue scale (VAS) rating from 0 (no pain) to 10 (worst pain imaginable)	Change from baseline at 3 weeks

Collaborators and Investigators

• Sponsor: Aalborg University
• Investigators: Principal Investigator: Line Bay Sørensen, PhD. stud., Aalborg University

Study record dates

Study Major Dates

• Study Start (Anticipated): February 18, 2019
• Primary Completion (Anticipated): June 30, 2019
• Study Completion (Anticipated): June 30, 2019

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 15, 2019
• First Posted (Actual): February 18, 2019

Study Record Updates

• Last Update Posted (Actual): February 18, 2019
• Last Update Submitted That Met QC Criteria: February 15, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Pain modulation; NGF-induced hyperalgesia; Exercise-induced ischemic pain; NGF pain model
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Ischemia; Hyperalgesia; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: N-2017-0007_S3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No