Effect of Ketoconazole on Breathlessness

NCT01378520 | Completed Phase 4 Results DMC

• 1 other identifier: CPHS22775
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Beta-endorphins, which are naturally occurring narcotic substances, have been shown to alter the perception of breathlessness. Oral ketoconazole, an antifungal antibiotic, increases blood levels of beta-endorphins. The study hypothesis is that oral ketoconazole will reduce ratings of breathlessness induced by resistive breathing loads.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

breathlessness; resistive load breathing; beta-endorphins

Outcome Measures

Primary Outcomes (2)

• Unpleasantness of Breathlessness

  The average of all ratings for the unpleasantness of breathlessness at equivalent times for each subject during Resistive Load Breathing (RLB). For example, if 1 subject provided 6 ratings during 6 minutes of RLB with Ketoconazole and 10 ratings during 10 minutes of RLB with inert powder, then ratings for unpleasantness through 6 minutes were used for analysis for that patient. This approach was used for all subjects to yield a total of 252 ratings for Ketoconazole and for inert powder. Subject rating of intensity of unpleasantness was obtained during RLB on a 100 mm Visual Analog Scale anchored at the bottom by "No Unpleasantness" and at the top by "Greatest Unpleasantness".

  At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)

• Intensity of Breathlessness

  The average of all ratings for the intensity of breathlessness at equivalent times for each subject during Resistive Load Breathing (RLB). For example, if 1 subject provided 6 ratings during 6 minutes of RLB with Ketoconazole and 10 ratings during 10 minutes of RLB with inert powder, then ratings for intensity through 6 minutes were used for analysis for that patient. This approach was used for all subjects to yield a total of 252 ratings for Ketoconazole and for inert powder. Subject rating of intensity of breathlessness was obtained at 1 minute intervals during RLB on a 100 mm Visual Analog Scale anchored at the bottom by "No Intensity" and at the top by "Greatest Intensity".

  At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)

Secondary Outcomes (1)

• Change in Level of B-endorphin Immunoreactivity

  At the end of resistance load breathing (4.5 hours after receiving the test article)

Study Arms (2)

ketoconazole

EXPERIMENTAL

600 mg ketoconazole

Drug: ketoconazole

inert powder

PLACEBO COMPARATOR

inert powder in capsule

Drug: inert powder

Interventions

ketoconazole DRUG

600 mg capsule oral once

Also known as: oral antifungal

ketoconazole

inert powder DRUG

oral once

Also known as: oral placebo

inert powder

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older;
• diagnosis of COPD;
• current or former smoker of at least 10 pack-years;
• post-bronchodilator FEV1 greater than or equal to 30% predicted and less than or equal to 80% predicted; post-bronchodilator ratio \< 70%

You may not qualify if:

• any concomitant disease that might interfere with study procedures;
• use of a drug that may cause a possible drug interaction with ketoconazole

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0001, United States

Location

Related Publications (2)

• Gifford AH, Mahler DA, Waterman LA, Ward J, Kraemer WJ, Kupchak BR, Baird JC. Neuromodulatory effect of endogenous opioids on the intensity and unpleasantness of breathlessness during resistive load breathing in COPD. COPD. 2011 Jun;8(3):160-6. doi: 10.3109/15412555.2011.560132. Epub 2011 Apr 22.

  PMID: 21513438 BACKGROUND

• Mahler DA, Gifford AH, Waterman LA, Ward J, Kraemer WJ, Kupchak BR, Harver A. Effect of increased blood levels of beta-endorphin on perception of breathlessness. Chest. 2013 May;143(5):1378-1385. doi: 10.1378/chest.12-1541.

  PMID: 23715032 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Dyspnea

Interventions

Ketoconazole; Antifungal Agents

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Donald A. Mahler, M.D.
• Organization: Dartmouth-Hitchcock

Donald.a.mahler@hitchcock.org

603 650-5533

Study Officials

• Donald A Mahler, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 22, 2011
• Study Start: June 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: June 1, 2018
• Results First Posted: November 14, 2013

Record last verified: 2018-05

Locations

US (1)