D-cycloserine + E-Cigarette for Smoking Cessation

Not currently recruiting at 1 trial location

Overseen By Perry Willette, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rose Research Center, LLC

Must not be taking: Antidepressants, Antipsychotics, Benzodiazepines, others

Disqualifiers: Coronary heart disease, High blood pressure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help smokers switch from regular cigarettes to Juul e-cigarettes. It combines d-cycloserine (an antibiotic) with a technique that changes reward values to see if quitting becomes easier. Participants take the medication and use the Juul for 12 weeks, aiming to fully switch within the first week. This trial suits those who smoke at least 10 cigarettes a day and are interested in switching to an e-cigarette. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial requires that you stop taking antidepressants, psychoactive medications, and certain other drugs like illegal drugs, chronic opiates, and tuberculosis medications. You also need to avoid using smokeless tobacco, cigars, pipes, hookah, e-cigarettes, and nicotine replacement therapy for at least 14 days before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that d-cycloserine is generally safe and well-tolerated. In a study with 29 participants over four weeks, d-cycloserine proved safe with few issues, meaning most people did not experience adverse reactions.

Regarding e-cigarettes like Juul, studies indicate that the vapor can affect the body, but these effects are usually less severe than those from smoking regular cigarettes. However, nicotine in any form, including e-cigarettes, can still harm the body, particularly the heart and lungs.

Overall, d-cycloserine has demonstrated a good safety record, and e-cigarettes are generally considered less harmful than regular smoking. However, consulting a healthcare provider is essential to determine if this trial is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard smoking cessation aids like nicotine replacement therapies, varenicline, or bupropion, the treatment combining D-cycloserine with e-cigarettes offers a unique approach. D-cycloserine is an antibiotic that also affects brain receptors involved in learning and memory, which may help retrain the brain's response to smoking cues. Researchers are excited because this combination has the potential to address both the physical and behavioral aspects of nicotine addiction, offering a new way to help smokers transition away from combustible cigarettes more effectively.

What evidence suggests that this treatment might be an effective treatment for smoking cessation?

Research has shown that d-cycloserine can help reduce cravings when combined with therapies that expose individuals to smoking triggers. This decrease in cravings is linked to a better chance of quitting smoking. One study found that using d-cycloserine with smoking reduction treatments improved the success of quitting smoking. Another study discovered that d-cycloserine can lower cravings and physical reactions to smoking cues. In this trial, participants will receive d-cycloserine alongside Juul e-cigarettes, which may help smokers switch from regular cigarettes to Juul e-cigarettes. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for smokers aged 22-65 who smoke more than 10 cigarettes a day and want to switch to an e-cigarette. They must have a compatible smartphone, breathe out enough carbon monoxide, and agree to the study's rules. People with serious health issues, high depression scores, plans to use other quit-smoking aids, certain heart conditions or drug uses can't join.

Inclusion Criteria

Willing and able to comply with the requirements of the study

Owns a smart phone with text message and data capabilities compatible with necessary surveys

I have been smoking 10 or more cigarettes daily for the past year.

Exclusion Criteria

Pregnant or nursing by self-report or positive pregnancy test

I have a history of heart problems, including heart disease or heart attack.

I have not used illegal or experimental drugs, chronic opiates, or TB medications in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take d-cycloserine and switch from combustible cigarettes to Juul e-cigarettes

12 weeks

Weekly check-ins

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Assisting Smokers to Switch to an e-Cigarette by Accelerating Learning of Adaptive Habits
• D-cycloserine

Trial Overview The study tests if taking d-cycloserine helps smokers switch from regular cigarettes to Juul e-cigarettes better than without it. It builds on previous research about changing rewards linked with smoking habits.

How Is the Trial Designed?

Group I: DCS with Juul e-cigarette Experimental Treatment 2 Interventions

d-cycloserine (DCS) 100 mg taken orally, once a day for six weeks. There will be a 50 mg dose taken the afternoon/evening prior to the first switch date (after enrollment) to ensure serum levels of the medication are available for the first switch to e-cigarette attempt. Participants will be instructed to use the Juul as often as they like during the 12 week period, and to switch completely to the Juul within 1 week. If, however, they do smoke any combustible cigarettes (CC), they will also be instructed to use the Juul immediately before each CC to relieve their craving as much as possible before smoking their usual brand. The Juul will also be the first product that they are instructed to use each morning. Smokers will be told to try to completely substitute Juul for CCs by the end of the first week of use.

D-cycloserine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Seromycin for:

• Tuberculosis

Approved in European Union as Seromycin for:

• Tuberculosis

Approved in Canada as Seromycin for:

• Tuberculosis

Who Is Running the Clinical Trial?

Rose Research Center, LLC

Lead Sponsor

Trials

17

Recruited

1,600+

Foundation for a Smoke Free World INC

Collaborator

Trials

15

Recruited

2,100+

Published Research Related to This Trial

Despite the availability of various smoking cessation pharmacotherapies, including nicotine replacement therapy and newer agents, less than 25% of smokers remain abstinent one year after treatment, highlighting the need for more effective options.

Combination therapies, particularly using nicotine replacement therapy alongside varenicline, have shown the highest rates of smoking cessation, while novel therapies like cytisine and N-acetylcysteine are emerging as promising alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Emerging Pharmacotherapies for Cessation of Tobacco Smoking. Gómez-Coronado, N., Walker, AJ., Berk, M., et al.[2018]

D-cycloserine treatment did not significantly affect cue-induced craving or cigarette smoking in cocaine-dependent smokers, despite a decrease in craving observed during the study.

The study, involving 29 participants over 4 weeks, showed that while D-cycloserine was safe and well-tolerated, cognitive-behavioral therapy alone led to significant reductions in smoking, indicating that this approach may be effective for individuals with concurrent cocaine and nicotine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of D-cycloserine on cue-induced craving and cigarette smoking among concurrent cocaine- and nicotine-dependent volunteers. Yoon, JH., Newton, TF., Haile, CN., et al.[2023]

In a randomized trial with 62 smokers, d-cycloserine (DCS) significantly reduced self-reported cravings for smoking cues compared to a placebo, particularly in participants who were reactive to cues and had no recent smoking-related reconditioning experiences.

DCS augmentation of cue exposure treatment (CET) showed a trend towards higher continuous tobacco abstinence rates (33% for DCS vs. 13% for placebo), suggesting its potential as a therapeutic aid in smoking cessation when used under optimal conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo-controlled randomized trial of D-cycloserine augmentation of cue exposure therapy for smoking cessation. Otto, MW., Pachas, GN., Cather, C., et al.[2020]

The study is testing a new treatment called Panic and Smoking Reduction Treatment (PSRT) that combines smoking cessation strategies with exposure therapy for smokers who experience panic attacks, as they are at a higher risk of relapse.

The trial will evaluate the effectiveness of adding d-cycloserine (DCS) to PSRT compared to a placebo, aiming to improve both short-term and long-term smoking cessation outcomes and understand the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing panic and smoking reduction treatment with d-cycloserine: Study protocol for a randomized controlled trial. Smits, JA., Kauffman, BY., Lee-Furman, E., et al.[2020]

In a pilot study with 25 smokers, the partial NMDA agonist D-cycloserine (DCS) significantly reduced reactivity to smoking cues when combined with cue exposure therapy, as shown by lower physiological responses and subjective urge-to-smoke ratings.

While DCS showed promise in reducing cue reactivity, it did not have a significant overall effect on smoking behavior at the one-week follow-up, indicating that further research is needed to explore its efficacy in promoting long-term abstinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

D-Cycloserine attenuates reactivity to smoking cues in nicotine dependent smokers: a pilot investigation. Santa Ana, EJ., Rounsaville, BJ., Frankforter, TL., et al.[2023]

In a pilot study involving 47 cocaine-dependent participants, the administration of 50 mg of D-cycloserine (DCS) did not significantly reduce craving or physiological responses to cocaine cues compared to a placebo, indicating that DCS may not be effective in this context.

Both treatment groups experienced a decrease in craving during cue exposure sessions, suggesting that the cue exposure protocol itself was effective in reducing reactivity to cocaine cues, regardless of DCS administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

D-cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence. Santa Ana, EJ., Prisciandaro, JJ., Saladin, ME., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6543820/

A Placebo-Controlled Randomized Trial of D-cycloserine ... Conclusions: DCS augmentation of CET can significantly reduce cue-induced craving, and such reductions in craving are meaningfully related to smoking cessation ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1551714416300477

Enhancing panic and smoking reduction treatment with d- ... Accordingly, in this treatment development study, we aim to test whether PSRT augmented by DCS would yield better smoking cessation outcomes relative to PSRT ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4885779/

Enhancing Panic and Smoking Reduction Treatment with ... Accordingly, in this treatment development study, we aim to test whether PSRT augmented by DCS would yield better smoking cessation outcomes relative to PSRT ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01062932

Investigation of Cycloserine as a Smoking Cessation ... A proof-of-concept study to examine effects of treatment with d-cycloserine for facilitating extinction of craving provoked by exposure to cigarette smoking ...

5. withpower.com withpower.com/trial/phase-2-smoking-cessation-8-2023-074c6

D-cycloserine + E-Cigarette for Smoking Cessation Research shows that D-cycloserine, when combined with cue exposure therapy, can reduce cravings and physiological reactions to smoking cues, potentially leading ...

6. globalheartjournal.com globalheartjournal.com/articles/10.5334/gh.1292

When Poison is Addictive – a WHF Policy Brief Numerous studies have demonstrated that nicotine can harm multiple organs, including the respiratory and cardiovascular systems.

7. goodday.health goodday.health/trials/5994703

CYCLE - GoodDay Planned use of an FDA-approved smoking cessation product during the study. 4. High Blood Pressure (systolic >150 mm Hg, diastolic >95 mm Hg) at screening.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7303083/

Electronic cigarette vapour moderately stimulates pro- ... These findings indicate that E-cigarette vapour moderately affects human DCs, but the effects are less pronounced than those reported for ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01907594

Study Details | Effects of Nicotine Replacement Therapy ... The aim of the proposed study is to assess whether DCS-facilitation of cue-exposure therapy improves abstinence among smokers on the nicotine patch seeking ...