The Role of N-acetyl-l-cysteine (NAC) as an Adjuvant to Opioid Treatment in Patients With Chronic Neuropathic Pain

• ClinicalTrials.gov Identifier: NCT01840345
• Recruitment Status: Completed
• First Posted: April 25, 2013
• Results First Posted: May 14, 2018
• Last Update Posted: May 14, 2018
• Sponsor: Virginia Commonwealth University
• Information provided by (Responsible Party): Virginia Commonwealth University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neuropathic Pain
• Intervention: Drug: N-acetyl-l-cysteine
• Enrollment: 11

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	N-acetyl-L-cysteine
Arm/Group Description	n-acetyl-l-cysteine 1200 mg BID x 4 weeks N-acetyl-l-cysteine: 1200 mg BID x 4 weeks
Period Title: Overall Study
Started	11
Completed	10
Not Completed	1

Baseline Characteristics

Arm/Group Title		N-acetyl-L-cysteine
Arm/Group Description		n-acetyl-l-cysteine 1200 mg BID x 4 weeks N-acetyl-l-cysteine: 1200 mg BID x 4 weeks
Overall Number of Baseline Participants		11
Baseline Analysis Population Description		One patient did not complete study so was not included in efficacy analysis
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	11 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	Female	7 63.6%
	Male	4 36.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	8 72.7%
	White	3 27.3%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Opioid Use
Description	The amount of opioid medication used was recorded. Then, it was converted to morphine equivalents (https://www.cms.gov/Medicare/Prescription-Drug-Coverage/PrescriptionDrugCovContra/Downloads/Opioid-Morphine-EQ-Conversion-Factors-March-2015.pdf). Opioid use was measured over a 2-week baseline period. Then, the average opioid medication use/week was calculated. This was compared to the average opioid medication use/week after 4 weeks of NAC.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-acetyl-L-cysteine
Arm/Group Description:	n-acetyl-l-cysteine 1200 mg BID x 4 weeks N-acetyl-l-cysteine: 1200 mg BID x 4 weeks
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: morphine equivalent dose
Baseline	101.24 (89.93)
4 weeks	104.56 (96.66)

2. Secondary Outcome

Title	Pain
Description	Pain intensity will be measured by using the 100-point Visual Analogue Scale, a 100-mm horizontal line with anchors of "no pain at all" (at 0) and "worst pain imaginable" (at 100mm) on which patients' pain intensities are measured.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-acetyl-L-cysteine
Arm/Group Description:	n-acetyl-l-cysteine 1200 mg BID x 4 weeks N-acetyl-l-cysteine: 1200 mg BID x 4 weeks
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: mm on 100 mm scale
Baseline	6.38 (1.58)
4 weeks	5.95 (1.96)

3. Secondary Outcome

Title	Mood
Description	Mood will be assessed by using the Patient Health Questionnaire (PHQ-9), a validated 9-question assessment of depression with total scores ranging from 0-27. Higher score = worse depression.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-acetyl-L-cysteine
Arm/Group Description:	n-acetyl-l-cysteine 1200 mg BID x 4 weeks N-acetyl-l-cysteine: 1200 mg BID x 4 weeks
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	10.4 (4.9)
4 weeks	9.7 (6.5)

4. Secondary Outcome

Title	Stress
Description	Stress will be measured by the Perceived Stress Scale ((PSS), a 10-item instrument for measuring the perception of stress, with total scores ranging from 0-40. Higher scores = higher perceived stress
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-acetyl-L-cysteine
Arm/Group Description:	n-acetyl-l-cysteine 1200 mg BID x 4 weeks N-acetyl-l-cysteine: 1200 mg BID x 4 weeks
Overall Number of Participants Analyzed	10
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	21.5 (3.6)
4 weeks	16.6 (1.4)

Adverse Events

Time Frame	A physical examination was done at Baseline. Then, adverse events were assessed at each study visit throughout the study and follow-up periods.
Adverse Event Reporting Description	All participants were asked about side effects and adverse events on a weekly basis, and any adverse events reported by the patients were evaluated by study staff.
Arm/Group Title	N-acetyl-L-cysteine
Arm/Group Description	n-acetyl-l-cysteine 1200 mg BID x 4 weeks N-acetyl-l-cysteine: 1200 mg BID x 4 weeks
All-Cause Mortality
	N-acetyl-L-cysteine
	Affected / at Risk (%)
Total	0/11 (0.00%)
Serious Adverse Events
	N-acetyl-L-cysteine
	Affected / at Risk (%)	# Events
Total	0/11 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	N-acetyl-L-cysteine
	Affected / at Risk (%)	# Events
Total	10/11 (90.91%)
Endocrine disorders
Sweating †	2/11 (18.18%)	2
Gastrointestinal disorders
Constipation †	2/11 (18.18%)	2
Diarrhea †	3/11 (27.27%)	4
Nausea †	4/11 (36.36%)	4
Gastroesophageal reflux †	5/11 (45.45%)	6
Loss of appetite †	2/11 (18.18%)	2
Dry mouth †	2/11 (18.18%)	2
chronic colonic ileus †	1/11 (9.09%)	1
Musculoskeletal and connective tissue disorders
Muscle tightness †	1/11 (9.09%)	1
Knee pain †	1/11 (9.09%)	1
Nervous system disorders
Sleepy †	1/11 (9.09%)	2
Headache †	1/11 (9.09%)	1
Insomnia †	1/11 (9.09%)	1
Skin and subcutaneous tissue disorders
Itching †	2/11 (18.18%)	2
Vascular disorders
Hypertension †	1/11 (9.09%)	1
† Indicates events were collected by systematic assessment

Limitations and Caveats

All adverse events reported regardless of causality

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Dace Svikis
• Organization: Virginia Commonwealth University
• Phone: (804) 827-1184
• EMail: dssvikis@vcu.edu

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT01840345
• Other Study ID Numbers: HM14748
• First Submitted: April 22, 2013
• First Posted: April 25, 2013
• Results First Submitted: February 15, 2018
• Results First Posted: May 14, 2018
• Last Update Posted: May 14, 2018