Doxycycline for Emphysema in HIV
(DEPTH Trial)
Recruiting in Palo Alto (17 mi)
+19 other locations
Overseen byMarshall J Glesby, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Approved in 5 Jurisdictions
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.
12345Is 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.
12678How 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.
12359Eligibility 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
+14 more
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.
+13 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: DoxycyclineExperimental Treatment1 Intervention
Doxycycline 100mg orally twice a day
Group II: PlaceboPlacebo Group1 Intervention
Matching placebo orally twice a day
Doxycycline is already approved in United States, European Union, Canada, Japan, Australia 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
🇦🇺 Approved in Australia as Doxycycline for:
- Acne
- Bacterial infections
- Chlamydia
- Gonorrhea
- Lyme disease
- Malaria
- Pneumonia
- Rosacea
- Urinary tract infections
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Tulane UniversityNew Orleans, LA
SUNY Downstate Medical SchoolBrooklyn, NY
University of PittsburghPittsburgh, PA
University of Texas, McGovern Medical SchoolHouston, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Weill Medical College of Cornell UniversityLead Sponsor
University of California, Los AngelesCollaborator
University of IowaCollaborator
University of MichiganCollaborator
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
[The efficacy of a maintenance dose of 100 mg doxycycline (Vibramycin) daily in bacterial infections of chronic bronchitis (author's transl)]. [2020]The efficacy and tolerance of a daily maintenance dose of 100 mg doxycycline (Vibramycin) was investigated in ambulant patients with chronic obstructive pulmonary disease (COPD) and bacterial infection by an open study with clinical, bacteriological and cytological control. The dosage was well tolerated and effective in the elimination of H. influenzae and pneumococci. A higher maintenance dose seems not to be necessary for this type of infections.
A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease. [2023]Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations, but there is a paucity of evidence for other antibiotic classes. Objectives: To assess whether 12-month use of doxycycline reduces the exacerbation rate in people with COPD. Methods: People with moderate to very severe COPD and an exacerbation history were recruited from three UK centers and randomized to 12 months of doxycycline 100 mg once daily or placebo. The primary study outcome was the exacerbation rate per person-year. Results: A total of 222 people were randomized. Baseline mean FEV1 was 1.35 L (SD, 0.35 L), 52.5% predicted (SD, 15.9% predicted). The median number of treated exacerbations in the year before the study was 2 (SD, 1-4). A total of 71% of patients reported two or more exacerbations, and 81% were already prescribed inhaled corticosteroids at baseline. The COPD exacerbation rate did not differ between the groups (doxycycline/placebo rate ratio [RR], 0.86; 95% confidence interval [CI], 0.67-1.10; P = 0.23). No difference was seen if only treated exacerbations or hospitalizations were considered. In preplanned subgroup analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR, 0.36; 95% CI, 0.15-0.85; P = 0.019) and in those with an eosinophil count <300 cells/μl (RR, 0.50; 95% CI, 0.29-0.84; P = 0.01). Health status measured by St. George's Respiratory Questionnaire was 5.2 points worse in the doxycycline group at 12 months (P < 0.007). Conclusions: Doxycycline did not significantly reduce the exacerbation rate, over 12 months, in participants with COPD who exacerbated regularly, but it may have benefitted those with more severe COPD or blood eosinophil counts <300 cells/μl. Clinical trial registered with www.clinicaltrials.gov (NCT02305940).
Effect of doxycyline in chronic obstructive pulmonary disease - An exploratory study. [2020]Various mechanisms, including oxidative stress, inflammation, and protease-antiprotease imbalance are proposed for the progressive decline in lung function in chronic obstructive pulmonary disease (COPD). Doxycycline, a broad spectrum tetracycline antibiotic, is reported to have non-antimicrobial matrix metalloproteinases (MMP) inhibitory action in various inflammatory conditions. The effect of doxycycline in COPD is hereby assessed in the present randomized prospective study.
[The therapeutic effect of doxycycline (Vibramycin) on pneumonia due to mycoplasma pneumoniae (author's transl)]. [2016]Tetracycline is expected to be as effective as erythromycin in the treatment of pneumonia due to Mycoplasma pneumoniae. In this clinical trial 12 cases with pneumonia due to Mycoplasma pneumoniae were given doxycycline (Vibramycin "Pfizer'), a long-acting derivative of tetracycline. Judging from time periods required for defervescence, improvement in symptoms such as cough and disappearance of shadows on chest X-ray, the therapeutic effect of doxycycline was excellent in 8 cases and good in 4 cases.
New uses for older antibiotics. The 'rediscovery' of four beneficial and cost-effective antimicrobials. [2019]Because of its intracellular mechanism of activity, excellent safety profile, and low cost, doxycycline is one of the most extensively used antibiotics in the world, and its use will increase as new applications are found. One of its most important uses is in treatment of bacterial community-acquired pneumonias, but it is also useful against atypical pneumonias and sexually transmitted disease. As zoonotic infections continue to increase around the world, doxycycline will occupy an increasingly prominent place. Minocycline shares doxycycline's favorable attributes and also has tissue-penetration characteristics that are important when therapeutic alternatives are few, as in MRSA. TMP-SMX is widely used to treat urinary and respiratory tract infections and for prophylaxis and treatment of P carinii infection. As the AIDS epidemic continues, its use will continue to grow, because it is also effective against other pathogens associated with AIDS. TMP-SMX is relatively underused for treating gram-negative bacteremias, especially nosocomial infections caused by nonaeruginosa pseudomonads. Metronidazole is a cost-effective antianaerobic component in treatment of intra-abdominal and pelvic infections, especially when it is combined with a once-a-day antibiotic.
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]Ninety-eight healthy subjects completed a double-blind, placebo-controlled, multiple-dose cross-over study to compare the incidence of gastrointestinal side effects of Doryx (Parke-Davis, Morris Plains, NJ) capsules (enteric-coated doxycycline hyclate pellets) and Vibramycin (Pfizer, New York, NY) capsules (doxycycline hyclate powder). Doryx produced statistically significantly fewer episodes of nausea, vomiting, stomach of abdominal discomfort, and decreased appetite than did Vibramycin. For every symptom, Vibramycin produced statistically significantly more symptom reports than did placebo. Although Doryx produced significantly more reports of nausea than did placebo, there was no significant difference for the other symptoms. Based on these results, Doryx is superior to Vibramycin when considering the incidence of gastrointestinal side effects.
[Vibravenös in infections of the biliary and respiratory tracts (author's transl)]. [2013]The clinical results of a European Vibravenös multicentre trial are reported as far as 227 patients with infections of the biliary tract and 185 patients with infections of the respiratory tract--mainly pneumonia--are concerned. In 203 of the 227 cases with biliary tract infections (=90%) and in 142 of the 185 cases with respiratory tract infections (=77%) the overall clinical result was good or very good. Toleration of Vibravenös was usually very good, only 4 patients had to be withdrawn from the trial because of side effects: in 3 cases an allergic skin reaction or pruritus occurred and in 1 patient local phlebitis developed at the injection site. Bacteriological tests performed on 71 patients showed that after broad usage doxycycline has an excellent antibacterial activity.
[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. [2013]Doxycyclin is one of the first efficacious depot antibiotics. It is used in two applications as Vibramycin (R) (peroral and Vibravenös (R) (parenteral). Doxycyclin has a favourable effect not only on different gram-positive and gram-negative bacteria but also on a lot of other germs as mycoplasms, rickettsias, protozoons and large viruses. The tissue invasions is a good one, because there is only a low fraction of free Doxycyclin and further a high lipid activity. Pharmacokinetic investigations of different age-groups show that good serum-levels can be reached because of the sensitivity of numerous germs. The levels are higher, as our experiences demonstrate, if the dose of 4 mg/kilo/weight is injected in two single doses. Our investigations are reported on 49 patients with diseases of the respiratory tract and on 25 patients with diseases of the urogenital tract. Doxycyclin was very useful especially in different forms of pneumonias. The results in infects of the urogenital tract are not so good ones. The compatibility of Doxycyclin can be characterised as very good for children.
Doxycycline concentrations in lung tissue, bronchial wall, and bronchial secretions. [2018]Doxycycline levels were measured in 44 patients undergoing lung surgery; 44 determinations were made on serum, 37 on resected lung tissue, 11 on bronchial wall, and 8 on bronchial secretions. The concentrations in lung tissue were, with few exceptions, higher than the serum concentrations, while those in homogenized bronchial wall specimens were slightly lower than the serum readings. All these concentrations were on average considerably higher than the minimum inhibitory concentrations for the pneumococcus and Haemophilus influenzae. The comparatively low bronchial secretion concentrations were accounted for by the surgical circumstances. All patients had been intensively trated pre-operatively, and showed no florid mucosal inflammation at the time of the operation: as inflammation subsides, so the antibiotic concentration in the bronchial secretion declines rapidly. The lung and bronchial wall tissue levels indicate that doxycycline has great promise in the treatment of pulmonary and bronchial disorders.