Doxycycline for Emphysema in HIV

(DEPTH Trial)

Recruiting at 19 trial locations

Overseen By Maile Karris, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Antiretrovirals

Must not be taking: Barbiturates, Carbamazepine, Phenytoin, others

Disqualifiers: Pulmonary infection, Serious illness, Cirrhosis, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 72 weeks

250 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if doxycycline will reduce progression of emphysema in people living with HIV. The secondary objectives are to examine the effects of doxycycline on change in quantity of emphysema, six minute walk distance, patient reported outcomes, ratio of forced expiratory volume in 1 second and forced vital capacity. Secondary objectives will also describe the safety and tolerability of doxycycline and determine if doxycycline is associated with development of antibiotic-resistant bacterial infections.

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 must be on stable antiretroviral therapy for at least 8 weeks and stable COPD therapy for at least 4 weeks before starting. You cannot use certain medications like barbiturates, carbamazepine, phenytoin, systemic retinoids, or antibiotics like doxycycline within specific time frames before the trial.

What evidence supports the effectiveness of the drug doxycycline for emphysema in HIV patients?

Doxycycline has been shown to be effective in treating bacterial infections in chronic lung conditions like COPD, and it may help reduce exacerbations in severe cases. Its ability to inhibit certain enzymes involved in inflammation could be beneficial in managing lung-related issues. ^{1 2 3 4 5}

Is doxycycline safe for humans?

Doxycycline is generally well-tolerated in humans, with some studies showing it can cause gastrointestinal issues like nausea and stomach discomfort. In rare cases, it may cause allergic reactions or skin issues, but overall, it is considered safe for use in treating various infections. ^{1 2 6 7 8}

How is the drug doxycycline unique for treating emphysema in HIV patients?

Doxycycline is unique because it not only acts as an antibiotic but also inhibits matrix metalloproteinases (MMPs), which are enzymes involved in inflammation and tissue breakdown, potentially offering benefits beyond traditional antibiotics in lung conditions like emphysema. ^{1 2 3 5 9}

Research Team

Marshall J Glesby, MD, PhD

Principal Investigator

Weill Medical College of Cornell University

Cathie Spino, ScD

Principal Investigator

University of Michigan

Robert J Kaner, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults over 30 with HIV and emphysema who are current or former smokers. They must have a stable HIV treatment, controlled virus levels, normal liver function tests, no recent serious illnesses or hospitalizations, and not be on certain medications that could interfere with the study.

Inclusion Criteria

CD4 cell count > 100 cells/mm3 within 90 days prior to the Entry/Baseline visit

Documentation of serum alpha-1-antitrypsin level above the lower limit of normal

DLCO measurements within 15% of each other

Exclusion Criteria

I have had C. difficile infection again within the last 30 days.

I am currently on, or might need, dialysis.

My liver is severely damaged and cannot function properly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 100 mg doxycycline or placebo orally twice a day

72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Doxycycline
• Placebo

Trial Overview The DEPTH Trial is testing whether doxycycline can slow down the progression of emphysema in people living with HIV. Participants will either receive doxycycline or a placebo to compare effects on lung health, exercise capacity, quality of life, and safety including antibiotic resistance.

Participant Groups

Group I: Doxycycline Experimental Treatment 1 Intervention

Doxycycline 100mg orally twice a day

Group II: Placebo Placebo Group 1 Intervention

Matching placebo orally twice a day

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

Approved in United States as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in European Union as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Canada as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Japan as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

A daily maintenance dose of 100 mg doxycycline was found to be effective and well tolerated in treating bacterial infections in patients with chronic obstructive pulmonary disease (COPD).

The treatment successfully eliminated bacteria such as H. influenzae and pneumococci, indicating that higher doses are not needed for these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of a maintenance dose of 100 mg doxycycline (Vibramycin) daily in bacterial infections of chronic bronchitis (author's transl)]. Eicke, R., Genz, U., Bartmann, K., et al.[2020]

In a study of 222 participants with moderate to severe COPD, 12 months of doxycycline treatment did not significantly reduce the overall exacerbation rate compared to placebo, indicating limited efficacy for the general COPD population.

However, doxycycline showed potential benefits in reducing exacerbations for patients with severe COPD and those with lower eosinophil counts, suggesting that specific subgroups may respond better to this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease. Allinson, JP., Vlies, BH., Brill, SE., et al.[2023]

In a study involving 60 COPD patients, adding doxycycline to standard therapy significantly reduced oxidative stress and inflammatory markers, suggesting its potential to improve lung function and quality of life.

Doxycycline's effects may be linked to its ability to inhibit matrix metalloproteinases (MMPs) and reduce pro-inflammatory cytokines like TNF-α, indicating a promising therapeutic role beyond its antibiotic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of doxycyline in chronic obstructive pulmonary disease - An exploratory study. Singh, B., Ghosh, N., Saha, D., et al.[2020]

In a clinical trial involving 12 patients with pneumonia caused by Mycoplasma pneumoniae, doxycycline (a tetracycline derivative) demonstrated excellent therapeutic effects in 8 cases and good effects in 4 cases.

The treatment led to significant improvements in symptoms, including reduced fever, alleviated cough, and resolution of chest X-ray abnormalities, indicating doxycycline's efficacy in treating this type of pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The therapeutic effect of doxycycline (Vibramycin) on pneumonia due to mycoplasma pneumoniae (author's transl)]. Izumikawa, K., Iwasaki, H., Ota, M., et al.[2016]

Doxycycline is a widely used antibiotic with a strong safety profile and low cost, effective against community-acquired pneumonia, atypical pneumonia, and sexually transmitted diseases, making it increasingly important as new applications are discovered.

Minocycline, similar to doxycycline, offers excellent tissue penetration for treating difficult infections like MRSA, while TMP-SMX is effective for urinary and respiratory infections and is gaining importance in treating infections related to AIDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New uses for older antibiotics. The 'rediscovery' of four beneficial and cost-effective antimicrobials. Cunha, BA.[2019]

In a study involving 98 healthy subjects, Doryx (enteric-coated doxycycline) was found to cause significantly fewer gastrointestinal side effects, such as nausea and abdominal discomfort, compared to Vibramycin (doxycycline powder).

While Doryx did lead to some reports of nausea compared to placebo, it overall had a better safety profile regarding gastrointestinal symptoms than Vibramycin, making it a preferable option for patients concerned about these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, multiple-dose, placebo-controlled, cross-over study to compare the incidence of gastrointestinal complaints in healthy subjects given Doryx R and Vibramycin R. Berger, RS.[2019]

In a European multicenter trial involving 412 patients, Vibravenös demonstrated a high overall clinical success rate, with 90% of patients with biliary tract infections and 77% of patients with respiratory tract infections reporting good or very good outcomes.

The treatment was generally well-tolerated, with only 4 patients experiencing side effects, including allergic reactions and local phlebitis, indicating a favorable safety profile for Vibravenös.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vibravenös in infections of the biliary and respiratory tracts (author's transl)]. Wickschrath, H.[2013]

Doxycycline is an effective antibiotic for treating various infections, particularly respiratory tract diseases like pneumonia, as demonstrated in a study involving 49 patients.

The drug shows good safety and compatibility, especially in children, and achieves effective serum levels when administered at a dose of 4 mg/kg in two injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. Weingärtner, L., Straube, D., Baum, W., et al.[2013]

In a study of 44 patients undergoing lung surgery, doxycycline concentrations in lung tissue were generally higher than in serum, suggesting effective local delivery of the antibiotic to the lungs.

The levels of doxycycline in lung and bronchial wall tissues were significantly above the minimum inhibitory concentrations needed to combat common respiratory pathogens, indicating its potential efficacy in treating pulmonary and bronchial disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxycycline concentrations in lung tissue, bronchial wall, and bronchial secretions. Gartmann, J.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[The efficacy of a maintenance dose of 100 mg doxycycline (Vibramycin) daily in bacterial infections of chronic bronchitis (author's transl)]. [2020]

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

A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effect of doxycyline in chronic obstructive pulmonary disease - An exploratory study. [2020]

4. Japan pubmed.ncbi.nlm.nih.gov

[The therapeutic effect of doxycycline (Vibramycin) on pneumonia due to mycoplasma pneumoniae (author's transl)]. [2016]

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

New uses for older antibiotics. The 'rediscovery' of four beneficial and cost-effective antimicrobials. [2019]

6. England pubmed.ncbi.nlm.nih.gov

A double-blind, multiple-dose, placebo-controlled, cross-over study to compare the incidence of gastrointestinal complaints in healthy subjects given Doryx R and Vibramycin R. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

[Vibravenös in infections of the biliary and respiratory tracts (author's transl)]. [2013]

8. Germany pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Doxycycline concentrations in lung tissue, bronchial wall, and bronchial secretions. [2018]