Varenicline + NRT for Smoking Cessation in PLWHA

(HTO Trial)

Recruiting at 1 trial location

Overseen By Robert Schnoll, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Pennsylvania

Must not be taking: Quit smoking medications

Disqualifiers: Substance abuse, Major depression, Psychosis, Bipolar, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 26

Duration: 24 weeks

340 Participants Needed

Trial Summary

What is the purpose of this trial?

The advent of anti-retroviral therapy (ART) for people living with HIV/AIDS (PLWHA) substantially improved life expectancy but has also led to the critical need to address modifiable risk factors associated with cancer and cardiovascular disease, such as tobacco smoking. HIV-infected smokers lose more life-years due to tobacco use than they do to their HIV infection. There have been relatively few studies of tobacco use treatments for PLWHA and systematic reviews show that there are insufficient data to conclude that tobacco dependence interventions that are efficacious in the general population are efficacious for PLWHA. Further, many studies in this area have lacked randomization and a control group, infrequently used an intent-to-treat (ITT) approach and biological verification of tobacco abstinence, and lacked post-treatment follow-up.10 What investigators do know thus far is that behavioral interventions and the nicotine patch yield moderate effects on cessation; and 2 recent placebo-controlled trials - one in France and one by this lab - found that varenicline is safe and effective for treating tobacco use among PLWHA, but yield quit rates that are substantially lower than those reported in the general population. Thus, there is a critical need to rigorously test novel ways to optimize tobacco cessation treatment for smokers with HIV.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use or have recently stopped using quit smoking medications within the last 14 days.

Is the combination of Varenicline and NRT safe for humans?

Varenicline, also known as Chantix, has been associated with serious side effects, including neuropsychiatric events (mental health issues), seizures, and interactions with alcohol. The FDA has issued warnings about these risks, so it's important to discuss the potential benefits and risks with a healthcare provider before starting this treatment. ^{1 2 3 4 5}

How does the drug Varenicline + NRT for smoking cessation in PLWHA differ from other treatments?

Varenicline combined with Nicotine Replacement Therapy (NRT) is unique because it targets smoking cessation through a dual approach: Varenicline reduces cravings and withdrawal symptoms by partially stimulating nicotine receptors in the brain, while NRT provides a controlled dose of nicotine to ease withdrawal. This combination may offer a more comprehensive strategy compared to using either treatment alone. ^{6 7 8 9 10}

Research Team

Robert Schnoll, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults over 18 who smoke daily, live near the study sites for at least 7 months, and can safely use varenicline or nicotine patches. Participants must be HIV positive with a viral load under 1000 copies/mL. Those with recent serious health issues, certain mental health conditions, or using other tobacco cessation methods cannot join.

Inclusion Criteria

I am over 18 years old.

You are living in the geographic area close to one of the sites for at least 7 months.

You have HIV and your viral load is less than 1000 copies/mL.

Exclusion Criteria

My high blood pressure is not under control.

History of epilepsy or seizure disorder requires study physician approval

I have had cancer, heart disease, stroke, or a heart attack in the last 6 months and need approval from the study doctor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varenicline or nicotine patch plus standard behavioral smoking cessation treatment with Managed Problem Solving adherence intervention

24 weeks

Regular visits for adherence monitoring and counseling

Follow-up

Participants are monitored for smoking abstinence and health outcomes post-treatment

26 weeks

Outcome assessments at week 26

Treatment Details

Interventions

• Nicotine patch
• Standard treatment
• Standard treatment + Managed Problem Solving (MAPS) adherence intervention
• Varenicline

Trial Overview The study tests if adding Managed Problem Solving (MAPS) to standard treatment helps people living with HIV/AIDS quit smoking more effectively than just standard care alone. It also examines the effectiveness of Varenicline and nicotine patches in this specific group.

Participant Groups

Group I: NMR-Tailored Medication & Standard Cessation Counseling + MAPS Experimental Treatment 3 Interventions

varenicline or nicotine patch plus standard behavioral smoking cessation treatment with Managed Problem Solving adherence intervention

Group II: Varenicline & Standard Cessation Counseling Active Control 2 Interventions

varenicline plus standard behavioral smoking cessation treatment

Nicotine patch is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Nicoderm for:

• Smoking cessation

Approved in European Union as Nicorette Patch for:

• Smoking cessation

Approved in Canada as NRT Patch for:

• Smoking cessation

Approved in Japan as Nicoderm for:

• Smoking cessation

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a randomized controlled trial, varenicline (Chantix) demonstrated a higher abstinence rate from smoking after one year compared to both bupropion SR (Zyban) and a placebo, indicating its efficacy in treating tobacco dependence.

Despite its effectiveness, varenicline has been associated with serious neuropsychiatric side effects, highlighting the importance of discussing potential risks and benefits with patients considering this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of nicotine dependence with Chantix (varenicline). Rankin, KV., Jones, DL.[2015]

Participants who chose varenicline (3,116 individuals) for tobacco cessation had higher abstinence rates at both 3 months (22%) and 6 months (17%) compared to those using nicotine replacement therapy (NRT) (13% at 3 months and 11% at 6 months), indicating that varenicline may be more effective in supporting quitting.

The study found that factors such as increasing age, having health insurance, and the number of counseling sessions were associated with higher rates of abstinence, particularly at 3 months, suggesting that these factors could enhance the effectiveness of quitline services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and abstinence outcomes among tobacco quitline enrollees using varenicline or nicotine replacement therapy. Biazzo, LL., Froshaug, DB., Harwell, TS., et al.[2015]

After the FDA issued warnings about neuropsychiatric side effects of varenicline, its use among veterans dropped significantly, decreasing from 6.2 to 1.0 per 1,000 smokers by July 2009, while nicotine replacement therapy (NRT) use increased, indicating a potential switch in treatment options.

Even after the FDA removed the warning in December 2016, varenicline prescribing did not return to pre-warning levels by December 2019, suggesting lasting impacts of the warnings on prescribing practices among veterans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in Incident Varenicline Prescribing Among Veterans Following the US Food and Drug Administration Drug Safety Warnings. Gerlach, LB., Van, T., Kim, HM., et al.[2023]

Smoking cessation is crucial for health, and psychiatric nurses should actively support patients in using therapies like varenicline (Chantix) to quit smoking.

Recent research has raised safety concerns about varenicline, including its potential links to neuropsychiatric side effects, seizures, and interactions with alcohol, which clinicians need to consider when recommending this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Psychopharmacology Update: Additional Safety Concerns for Using Varenicline (Chantix) for Smoking Cessation Treatment. Tobin, TJ., Tobin, ML.[2018]

In a study of 139 long-term nicotine replacement therapy users, varenicline combined with counseling significantly improved the quit rate at 12 weeks (64.3% for varenicline vs. 40.6% for placebo), indicating its efficacy in helping users stop NRT.

Participants taking varenicline experienced lower withdrawal symptoms compared to those on placebo, suggesting that varenicline not only aids in quitting but also makes the process more comfortable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial. Tønnesen, P., Mikkelsen, K.[2015]

Intralesional cidofovir was administered to a renal transplant patient with numerous palmar warts, with seven injections given at four-week intervals, demonstrating its potential effectiveness in treating stubborn warts in immunocompromised individuals.

The results suggest that cidofovir could be a promising treatment option for cutaneous warts in patients with weakened immune systems, such as those who have undergone kidney transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intralesional cidofovir in the treatment of cutaneous warts in a renal transplant patient. Blouin, MM., Cloutier, R., Noël, R.[2018]

In a study involving 37 immunocompetent subjects, the nitric-zinc complex showed a 90% complete cure rate for external genital warts and difficult-to-treat warts after one to four applications, demonstrating its efficacy.

The treatment was well tolerated with no serious adverse events reported, indicating it is a safe option for patients suffering from these types of warts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of nitric-zinc complex in the treatment of external genital warts and "difficult-to-treat" warts: a "proof of concept", prospective, multicentre, open study. Cusini, M., Micali, G., Lacarrubba, F., et al.[2015]

Interferon alpha is currently the only antiviral/immunomodulatory drug approved for treating genital warts, but it has limitations such as high cost, systemic side effects, and slow action.

New antiviral/immunomodulatory drugs like imiquimod and cidofovir show promise in effectively treating warts while also aiming to reduce the recurrence of HPV, addressing the shortcomings of existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic approaches to papillomavirus infections. Baker, GE., Tyring, SK.[2019]

Topical cidofovir has been shown to be an effective treatment for non-genital warts, achieving clearance in 55.2% of patients, based on a review of 603 cases.

The treatment demonstrated a favorable safety profile, with only 17.4% of patients experiencing local side effects, and no recurrence of lesions reported within a follow-up period averaging 15.8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cidofovir in the Management of Non-Genital Warts: A Review. Cook, MK., Hagen, EM., Feldman, SR.[2023]

In a study involving 269 wart lesions treated with either a 0.5% podophyllotoxin cream or solution, both treatments significantly reduced wart size, with complete clearance achieved in 63% of patients in both groups after 8 weeks.

The study found no additional clinical benefits of using the cream formulation over the solution, as both had similar efficacy and side effects in treating external genital warts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-blind study of podophyllotoxin cream 0.5% and podophyllotoxin solution 0.5% in male patients with genital warts. Petersen, CS., Agner, T., Ottevanger, V., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of nicotine dependence with Chantix (varenicline). [2015]

2. England pubmed.ncbi.nlm.nih.gov

Characteristics and abstinence outcomes among tobacco quitline enrollees using varenicline or nicotine replacement therapy. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Trends in Incident Varenicline Prescribing Among Veterans Following the US Food and Drug Administration Drug Safety Warnings. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Clinical Psychopharmacology Update: Additional Safety Concerns for Using Varenicline (Chantix) for Smoking Cessation Treatment. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Intralesional cidofovir in the treatment of cutaneous warts in a renal transplant patient. [2018]

7. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of nitric-zinc complex in the treatment of external genital warts and "difficult-to-treat" warts: a "proof of concept", prospective, multicentre, open study. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Therapeutic approaches to papillomavirus infections. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Cidofovir in the Management of Non-Genital Warts: A Review. [2023]

10. England pubmed.ncbi.nlm.nih.gov

A single-blind study of podophyllotoxin cream 0.5% and podophyllotoxin solution 0.5% in male patients with genital warts. [2019]