Effect of Ketoconazole on Breathlessness

Chronic Obstructive Pulmonary Disease Clinical Trial

— KetoRLB  

Official title:

The Effect of Ketoconazole on Breathlessness During Resistive Load Breathing in Patients With Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01378520
• Other study ID #: CPHS22775
• Status: Completed
• Phase: Phase 4
• Start date: June 2011
• Est. completion date: February 2012

Study information

• Verified date: May 2018
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Beta-endorphins are naturally occurring narcotic substances (like morphine) that are released by the brain under stressful conditions, such as exercise and when breathing through a resistive load (a tube containing fine wire mesh). In one study of 8 patients with coronary artery disease, ketoconazole, an oral medication used to treat fungal infections, was administered (1,200 mg at 12 midnight and 600 mg at 6 am) and increased blood levels of beta-endorphins five fold. In a recent study performed at Dartmouth-Hitchcock Medical Center, we found that ketoconazole increased blood levels of beta-endorphins in all eight patients with chronic obstructive pulmonary disease (COPD). Mean values increased by 2.5 times at four hours compared with baseline values (p = 0.0078). Based on this significant response, we propose to study the effect of ketoconazole on patients' perception of breathlessness induced by resistive breathing loads in a randomized clinical trial. The hypothesis of the study is that ketoconazole will reduce ratings of breathlessness as mediated by the increased levels of beta-endorphins.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• 50 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%

Exclusion Criteria:

• any concomitant disease that might interfere with study procedures;

• use of a drug that may cause a possible drug interaction with ketoconazole

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Dyspnea
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• ketoconazole
600 mg capsule oral once
• inert powder
oral once

Locations

Country	Name	City	State
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Change in Level of B-endorphin Immunoreactivity	Change between pre-treatment and post treatment serum levels of beta-endorphin immunoreactivity measured in pmol/L	At the end of resistance load breathing (4.5 hours after receiving the test article)