This non-randomised open-label prospective pilot study evaluates the safety and efficacy of inhalations of ultra-low doses of alkylating drug melphalan for the treatment of non-cystic fibrosis bronchiectasis. All patients will receive 0,1 mg of melphalan in 5 daily inhalations 1 time per day.
It was previously shown that in ultra-low (more than 100 times lower than conventional therapeutic) doses inhalations of alkylating drug (melphalan) are effective in severe steroid-resistant bronchial asthma, a form of the disease often characterized by neutrophilic type of inflammation. The exacerbation frequency reduced after the treatment, steroid-sparing effect was shown, morphological signs of bronchial epithelial regeneration were revealed and quality of life of asthmatic patients, treated with ultra-low doses of melphalan, improved. In preclinical studies and studies with volunteers, it was found that inhalations of ultra-low doses of melphalan do not have cytotoxic properties, but have local and systemic anti-inflammatory effects and decrease the activation of lymphocytes due to blockade of heavy β-chain of the interleukin (IL)-2 surface receptor. In addition, in ultra-low concentrations, alkylating agents are able to disrupt the cell signalling through the receptor for tumor necrosis factor, thereby exerting a protective effect from the cytotoxic activity of tumor necrosis factor (TNF)-α, which leads to the anti-inflammatory response. It can be assumed that the inhalation use of ultra-low doses of melphalan can be effective in patients with bronchiectasis, as in a disease characterized by a neutrophilic type of inflammation, leading to the improvement of quality of life, increasing the time to the first exacerbation and decreasing of exacerbation frequency.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Inhalations with low doses of Melphalan for 5 consequent days
Kirill Zykov
Moscow, Russia
RECRUITINGFrequency of drug-related side effects.
The evaluation of side-effects, typical for the conventional therapeutic doses of melphalan (cough, bronchospasm, pulmonary fibrosis, interstitial pneumonitis; anorexia, gastrointestinal bleeding, ulcers of the stomach and duodenum, stomatitis, nausea, vomiting, esophagitis, diarrhea; myelodepression (leukopenia, thrombocytopenia, anemia), hemolytic anemia, bleeding and hemorrhage, vasculitis, veno-occlusive lesions, asystole; impaired urination, hematuria, hyperuricemia, nephropathy, edema, proteinuria, ovarian hypofunction, amenorrhea, azoospermia; anaphylaxis, anaphylactic shock, Quincke's edema, urticaria, skin rash, itching; dysfunction of the central nervous system, pain (back, side pain), the development of infections, fever, chills, alopecia, an increase in the concentration of 5-hydroxyindoleacetic acid, necrosis of the perivascular space, a feeling of heat and / or tingling at the injection site)
Time frame: 6 months from the first inhalation
The changes of The St George's Respiratory Questionnaire (SGRQ)
The evaluation of changes in quality of life with the SGRQ questionnaire (50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction). Scores are calculated for three domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. Lower score means a better the quality of life. A minimum change in score of 4 units was established as clinically relevant.
Time frame: Day1 - Day 177 (±7 days)
The changes of The Quality of Life-Bronchiectasis (QOL-B) questionnaire
The Quality of Life-Bronchiectasis (QOL-B), a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis bronchiectasis, contains 37 items on 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).The minimal important difference score for the Respiratory Symptoms scale is 8.0 points. Higher scores represent a better quality of life.
Time frame: Day1 - Day 177 (±7 days)
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