Minocycline and Tobacco Craving in Smokers With Schizophrenia

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Tobacco Use
• Intervention / Treatment: Drug: Minocycline; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Maryland Psyciatric Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Questionnaire for Smoking Urges-Brief	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.	Baseline, Week 1, and Week 2

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2017
• Primary Completion (Actual): July 23, 2019
• Study Completion (Actual): July 23, 2019

Study Registration Dates

• First Submitted: November 15, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 18, 2016

Study Record Updates

• Last Update Posted (Actual): January 6, 2022
• Last Update Submitted That Met QC Criteria: January 4, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: HP-00072110; 4K23DA034034-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: This study was funded prior to the NIH requirements for sharing of IPD, therefore is not within our budget.

Drug and device information, study documents

• 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