Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation (1207)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Annie Umbricht, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01685996
First received: September 12, 2012
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

About 20.6 % of the US population smokes cigarettes. This group includes nicotine dependent smokers who are resistant to current smoking cessation treatments. Varenicline is a smoking cessation medication found in meta-analytic reviews to be superior to other smoking cessation treatments, but 56% of patients who take varenicline do not quit. One strategy to increase quit rates may be to administer a second medication to augment the efficacy of varenicline. The anti-epileptic medication zonisamide is a good candidate for adjunct treatment as it increases dopaminergic tone, normalizes glutamate homeostasis, potentiates GABA release. Zonisamide improves sleep and promotes weight loss, two prominent issues not addressed by varenicline. Finally, the PI of this proposal has documented unpleasant changes in the taste of cigarettes and reductions in nicotine withdrawal among smokers receiving zonisamide as part of another clinical trial. The proposed study will explore the efficacy of varenicline + zonisamide for smoking cessation in a controlled, clinical trial. Eligible participants (n=60) will be smokers (>10 cig/day for >1 year) seeking treatment. They will be randomly assigned to receive varenicline + double-blind zonisamide or placebo for a 10-weeks. Participants will visit the clinic weekly to receive medications and smoking cessation counseling and to complete self-report questionnaires. Smoking status will be assessed via weekly urinalysis testing for cotinine (abstinence: <200ng/ml). Cotinine is a sensitive indicator of smoking status with a longer half-life then carbon monoxide (CO) and is more likely to detect low or intermittent smoking. The study hypothesis is that participants who receive the combination zonisamide + varenicline will achieve greater smoking abstinence compared to varenicline alone. The primary outcome measure will be the 4-week rate of biochemically-confirmed continuous smoking abstinence during weeks 7-10. Secondary outcomes will include self-reported rates of smoking, subjective effects of cigarettes, weight change from baseline to week 10, sleep quality, and nicotine withdrawal severity. This study will advance the science and clinical treatment of smoking cessation, and will provide the prerequisite data to develop a larger scale clinical trial evaluation of the combination zonisamide + varenicline for smoking cessation.


Condition Intervention Phase
Nicotine Dependence
Drug: zonisamide
Drug: placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • smoking abstinence [ Time Frame: weeks 7-10 ] [ Designated as safety issue: No ]
    The primary outcome measure for this study will be the 4-week rate of biochemically-confirmed continuous smoking abstinence during weeks 7-10 of the intervention


Secondary Outcome Measures:
  • nicotine withdrawal symptom severity [ Time Frame: weeks 3-10 ] [ Designated as safety issue: No ]
    nicotine withdrawal symptoms will be monitored weekly


Other Outcome Measures:
  • sleep quality [ Time Frame: weeks 3-10 ] [ Designated as safety issue: No ]
    sleep diary will be kept, and self-reported sleep quality will be measured weekly


Estimated Enrollment: 200
Study Start Date: September 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: zonisamide
participants will receive zonisamide capsules (up to 300 mg) to take once a day.
Drug: zonisamide
In addition to zonisamide vs placebo treatment, varenicline tablets will be dispensed with specific instructions to take at the recommended doses for smoking cessation Participants will receive brief smoking cessation counseling and referral to a quitline
Other Name: zonegran®
Placebo Comparator: Placebo
Participants will receive placebo capsules to take once a day
Drug: placebo

Detailed Description:

Hughes JR, Rennard SI, Fingar JR, Talbot SK, Callas PW, Fagerstrom KO. Efficacy of varenicline to prompt quit attempts in smokers not currently trying to quit: A randomized placebo-controlled trial. Nicotine Tob Res. 2011 Oct; 13(10): 955-964.

Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2010 Dec 8; (12)(12): CD006103.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages 18 - 65 years old; smoking > 10 cigarettes per day for > 1 year
  • Desire to quit smoking
  • Provide a cotinine positive urine sample
  • Commitment to come to the clinic once a week for the 10-week study duration

Exclusion Criteria:

  • Allergy to varenicline or sulfonamide drugs (e.g., trimetoprim/sulfamethoxazole, zonisamide or topiramate);
  • Renal insufficiency (eGFR < 60 mL)
  • Renal tubular acidosis
  • History of nephrolithiasis
  • Unexplained hematuria
  • Transaminase elevations > 3 times the ULN
  • BMI < 19
  • Diabetes mellitus
  • Respiratory insufficiency
  • Asthma requiring medication
  • Heart failure
  • Chronic diarrhea predisposing to acidosis
  • Glaucoma, family history of glaucoma, one-sided blindness
  • History of seizures or use of anticonvulsant medications (not including sedatives)
  • HIV infection on HAART medication (or CD4 T cell count < 200 /mL)
  • History of serious psychiatric disorder: psychosis, dementia, depression requiring medication in last 6 months, suicidal or homicidal ideation, evidence of violent behavior in the last 6 months.
  • Recent use (last 30 days) of bupropion, nortriptyline, or clonidine
  • Recent use (last 30 days) of Nicotine Replacement Products that would interfere with urine cotinine testing
  • Use of tobacco products other than cigarettes
  • For female participants, pregnancy, lactation, or refusal to use an effective method of contraception.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685996

Locations
United States, Maryland
Behavioral Pharmacology Research Unit
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Annie Umbricht, M.D. Assistant Professor Behavioral Pharmacology Research Unit The Johns Hopkins University School of Medicine 5510 Nathan Shock Drive Baltimore, MD 21224 tel: 410-550-1917 fax:410-550-0011 annieumbricht@jhu.edu
  More Information

No publications provided

Responsible Party: Annie Umbricht, Assistant Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01685996     History of Changes
Other Study ID Numbers: R21 DA034164
Study First Received: September 12, 2012
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
tobacco
smoking cessation
nicotine
cigarettes
nicotine withdrawal

Additional relevant MeSH terms:
Varenicline
Zonisamide
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Antioxidants
Protective Agents

ClinicalTrials.gov processed this record on September 30, 2014