Minocycline and Tobacco Craving in Smokers With Schizophrenia

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT02968602
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 32
• Location: 1
• Arms: 2
• Actual Duration (Months): 27.7
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Craving for cigarettes is an important aspect that leads to challenges with smoking cessation. Persons with schizophrenia are more likely to smoke and to be heavier smokers than persons without schizophrenia, and may experience craving differently as well. Minocycline is an antibiotic medication that may impact craving. We will conduct a two-week randomized, double-blind, placebo-controlled, parallel group pilot study to investigate the effects of minocycline vs. placebo on craving and smoking behaviors in smokers with schizophrenia. Participants will take minocycline or matching placebo for two weeks. Participants will be assessed on aspects of craving and smoking behavior at baseline and after 1 and 2 weeks of minocycline or placebo treatment.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Tobacco Use	Drug: Minocycline; Other: Placebo	Phase 4

Detailed Description

Nicotine dependence is high in schizophrenia; nearly three times more prevalent than the general population. In smokers with schizophrenia, the risk of all-cause mortality is doubled and cardiovascular mortality risk is twelvefold higher than nonsmokers. Many factors influence smoking in persons with schizophrenia, but predictors of craving and smoking behavior are not well established. Craving is a major contributor to smoking behaviors, and, importantly, is a predictor of relapse risk. Since craving may precede relapse, it can be advantageous as a screening tool for those attempting cessation. In addition, focusing on treatments aimed to reduce craving may lead to better therapeutic targets. Minocycline may affect craving, perhaps due to inhibition of nitric oxide (NO) formation, as NO acts as a second messenger for glutamate and dopamine receptors. NO also facilitates the effects of nicotine in the reward circuit, and blockade of NO has been demonstrated to eliminate nicotine abstinence symptoms in rats. A small study has demonstrated that minocycline reduces cigarette craving in human subjects without severe mental illness. The investigators will conduct a two-week randomized, double-blind, placebo-controlled, parallel group pilot study to investigate the effects of minocycline vs. placebo on craving and indicators of smoking intensity in smokers with schizophrenia. Participants will take minocycline up to 200 mg daily or matching placebo for two weeks. Participants will complete cigarette cue-elicited craving platforms and related assessments at baseline, and after 1 and 2 weeks of minocycline or placebo treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Minocycline and Tobacco Craving in Smokers With Schizophrenia
• Actual Study Start Date: Mar 31, 2017
• Actual Primary Completion Date: Jul 23, 2019
• Actual Study Completion Date: Jul 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Minocycline Participants will take 50 mg minocycline capsules twice daily for 1 week, then take 100 mg capsules twice daily for 1 week.	Drug: Minocycline; Minocycline capsules taken twice daily for two weeks.
Placebo Comparator: Placebo Participants will take capsules that match active drug, but contain no active ingredients, twice daily for week 1, and then will take capsules that match active drug, but contain no active ingredients, twice daily for week 2.	Other: Placebo; Placebo capsules taken twice daily for two weeks.

Outcome Measures

Primary Outcome Measures

1. Questionnaire for Smoking Urges-Brief [Baseline, Week 1, and Week 2]

   This is a 10-item assessment used to measure craving to smoke and used in studies of smokers with schizophrenia. This scale has a score range from 0-100The change in QSU-Brief craving scores between time points (baseline to week 1, and baseline to week 2) will be assessed. The change in scores between the two timepoints will be calculated. The higher the score the stronger the urge to smoke is.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• DSM-IV or DSM-5 diagnosis of schizophrenia or schizoaffective disorder

• Male or Female

• Age: 18 to 65 years

• Caucasian or Non-Caucasian

• Smoke at least 10 cigarettes daily

• Urine cotinine level ≥ 100 ng/ml (NicAlert® reading ≥ 3)

• Agrees to wear a head mounted display (HMD) for up to 45 minutes

• Able to complete the Evaluation to Sign Consent (ESC) with minimum score of 80%

Exclusion Criteria

• History of organic brain disease

• DSM-IV diagnosis of Alcohol or Substance Dependence within the last six months (except nicotine) or DSM-5 diagnosis of Substance Use Disorder in the last six months (except nicotine)

• DSM-IV diagnosis of Alcohol or Substance Abuse within the last one month (except nicotine) or DSM-5 diagnosis of Substance Use Disorder in the last six months (except nicotine)

• Pregnancy or lactation

• Severe liver dysfunction (LFT 3X upper limit of normal)

• Previous known hypersensitivity to tetracyclines

• Current treatment with tetracycline or derivative

• Treatment with oral contraceptives (unless a second form of birth control is used and documented)

• Treatment with cholestyramine or colestipol

• Treatment with Urinary alkalinizers (e.g., sodium lactate, potassium citrate)

• Treatment with warfarin

• Treatment with bupropion, varenicline, or nicotine replacement products in the month prior to study inclusion

• Less than two months treatment of adjunctive medications AND less than one month on same dose: beta blockers, antidepressants, mood stabilizers, antianxiety medications.

• Medical condition whose pathology or treatment would significantly increase the risk associated with the proposed protocol.

• History of head injury, seizures, or stroke

• Positive urine toxicology screen for substances of non-therapeutic use prior to craving assessments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maryland Psyciatric Research Center	Catonsville	Maryland	United States	21228

Sponsors and Collaborators

• University of Maryland, Baltimore
• National Institute on Drug Abuse (NIDA)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 1, 2020

More Information

Publications

None provided.

• Responsible Party: Deanna Kelly, Professor, Chief Treatment Research Program, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT02968602
• Other Study ID Numbers: HP-00072110; 4K23DA034034-04
• First Posted: Nov 18, 2016
• Last Update Posted: Jan 6, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Schizophrenia; Minocycline

Study Results

Participant Flow

Arm/Group Title	Minocycline	Placebo
Arm/Group Description	Participants will take 50 mg minocycline capsules twice daily for 1 week, then take 100 mg capsules twice daily for 1 week. Minocycline: Minocycline capsules taken twice daily for two weeks.	Participants will take capsules that match active drug, but contain no active ingredients, twice daily for week 1, and then will take capsules that match active drug, but contain no active ingredients, twice daily for week 2. Placebo: Placebo capsules taken twice daily for two weeks.
Period Title: Overall Study
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Minocycline	Placebo	Total
Arm/Group Description	Participants will take 50 mg minocycline capsules twice daily for 1 week, then take 100 mg capsules twice daily for 1 week. Minocycline: Minocycline capsules taken twice daily for two weeks.	Participants will take capsules that match active drug, but contain no active ingredients, twice daily for week 1, and then will take capsules that match active drug, but contain no active ingredients, twice daily for week 2. Placebo: Placebo capsules taken twice daily for two weeks.	Total of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	16 100%	32 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.43 (11.32)	43.38 (8.22)	43.4 (9.74)
Sex: Female, Male (Count of Participants)
Female	3 18.8%	3 18.8%	6 18.8%
Male	13 81.3%	13 81.3%	26 81.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	10 62.5%	10 62.5%	20 62.5%
White	6 37.5%	5 31.3%	11 34.4%
More than one race	0 0%	1 6.3%	1 3.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%	16 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Questionnaire for Smoking Urges-Brief
Description	This is a 10-item assessment used to measure craving to smoke and used in studies of smokers with schizophrenia. This scale has a score range from 0-100The change in QSU-Brief craving scores between time points (baseline to week 1, and baseline to week 2) will be assessed. The change in scores between the two timepoints will be calculated. The higher the score the stronger the urge to smoke is.
Time Frame	Baseline, Week 1, and Week 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Minocycline	Placebo
Arm/Group Description	Participants will take 50 mg minocycline capsules twice daily for 1 week, then take 100 mg capsules twice daily for 1 week. Minocycline: Minocycline capsules taken twice daily for two weeks.	Participants will take capsules that match active drug, but contain no active ingredients, twice daily for week 1, and then will take capsules that match active drug, but contain no active ingredients, twice daily for week 2. Placebo: Placebo capsules taken twice daily for two weeks.
Measure Participants	16	16
Baseline to week 1	42.1429 (16.23319)	38.6429 (18.46663)
Baseline to week 2 (Endpoint)	43.4286 (18.03720)	36.8571 (17.81467)

Adverse Events

Time Frame	2 weeks
Arm/Group Title	Minocycline		Placebo
Arm/Group Description	Participants will take 50 mg minocycline capsules twice daily for 1 week, then take 100 mg capsules twice daily for 1 week. Minocycline: Minocycline capsules taken twice daily for two weeks.		Participants will take capsules that match active drug, but contain no active ingredients, twice daily for week 1, and then will take capsules that match active drug, but contain no active ingredients, twice daily for week 2. Placebo: Placebo capsules taken twice daily for two weeks.
All Cause Mortality
	Minocycline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Minocycline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Minocycline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/16 (43.8%)		7/16 (43.8%)
Gastrointestinal disorders
Vomiting	0/16 (0%)	0	1/16 (6.3%)	1
Constipation	2/16 (12.5%)	2	0/16 (0%)	0
Nausea	0/16 (0%)	0	1/16 (6.3%)	1
General disorders
Arthritus	1/16 (6.3%)	1	0/16 (0%)	0
Hypersalavation	0/16 (0%)	0	2/16 (12.5%)	5
Sedation	2/16 (12.5%)	2	3/16 (18.8%)	3
Restlessness	2/16 (12.5%)	3	0/16 (0%)	0
Loss of Appetite	2/16 (12.5%)	2	0/16 (0%)	0
Insomnia	2/16 (12.5%)	2	0/16 (0%)	0
Malaise	2/16 (12.5%)	2	0/16 (0%)	0
Dizziness	2/16 (12.5%)	2	0/16 (0%)	0
Stiffness	1/16 (6.3%)	1	0/16 (0%)	0
Uticaria	1/16 (6.3%)	1	0/16 (0%)	0
Somatic Concern	0/16 (0%)	0	1/16 (6.3%)	1
Back Pain	0/16 (0%)	0	1/16 (6.3%)	1
Headache	1/16 (6.3%)	1	0/16 (0%)	0
Hostility	1/16 (6.3%)	1	0/16 (0%)	0
Tremor	1/16 (6.3%)	1	0/16 (0%)	0
"Zoning out"	0/16 (0%)	0	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.