Danazol for Low Blood Counts in Liver Cirrhosis
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Southern California
Must not be taking: Hormone stimulants, Bone marrow stimulants
Disqualifiers: Hepatitis B, HIV, Hormone-sensitive malignancy, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing danazol, a medication taken by mouth, to see if it can help people with liver disease and low blood cell counts. Danazol may work by changing hormone levels to increase blood cell production. It has been used to treat certain bleeding conditions, showing long-term benefits.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications, such as hormone stimulants, hormone blockers, bone marrow stimulants, and systemic immunosuppressive medications. If you are on corticosteroids, you must be on a stable dose of 5 mg or less of prednisone (or equivalent) for at least 8 weeks before joining the trial.
What data supports the effectiveness of the drug Danazol for low blood counts in liver cirrhosis?
There is no direct data on Danazol for low blood counts in liver cirrhosis, but similar treatments like anabolic steroids have shown to improve albumin turnover in cirrhosis, which might suggest potential benefits.
12345How is the drug Danazol unique in treating low blood counts in liver cirrhosis?
Danazol is unique because it is a synthetic steroid that can increase blood cell production, which may help address low blood counts in liver cirrhosis, a condition where traditional treatments are limited. Unlike other treatments that focus on managing symptoms or complications, Danazol directly influences blood cell production, potentially offering a novel approach for patients with this condition.
678910Eligibility Criteria
Adults over 18 with compensated liver cirrhosis (Child-Pugh class A/B) and low blood counts, who can consent to treatment. They must not be pregnant or breastfeeding, agree to use effective contraception if of childbearing potential, and have no history of certain conditions like heart failure or uncontrolled diseases. Excludes those with hepatitis B, recent liver decompensation events, HIV infection, high bilirubin levels, or on specific medications.Inclusion Criteria
- Thrombocytopenia defined as platelet count ≤ 100,000/mm3 measured on two separate occasions at least 3 months apart within 6 months of enrollment
I am 18 or older and can give my consent.
I do not have telomere mutations that increase their function.
+14 more
Exclusion Criteria
I have cirrhosis due to chronic hepatitis B or have had hepatitis B.
Alanine aminotransferase and/or aspartate aminotransferase >3x upper limit of normal
Total bilirubin or direct bilirubin >2.5 x upper limit of normal
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive danazol 600 mg per day by mouth for treatment of cytopenias in patients with cirrhosis
24 months
Visits every 3 months for blood tests and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing the safety and effectiveness of a drug called Danazol at a dose of 600 mg daily for two years in patients with liver cirrhosis experiencing low blood cell counts. It aims to enroll 10 patients including those without telomere mutations.
1Treatment groups
Experimental Treatment
Group I: Danazol in Treatment of CytopeniasExperimental Treatment1 Intervention
AGENT: Danazol 600mg, Oral, Daily for 24 months
Danazol is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Danocrine for:
- Endometriosis
- Hereditary Angioedema
- Fibrocystic Breast Disease
🇪🇺 Approved in European Union as Danol for:
- Endometriosis
- Hereditary Angioedema
- Fibrocystic Breast Disease
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Keck Hosital of USCLos Angeles, CA
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Who Is Running the Clinical Trial?
University of Southern CaliforniaLead Sponsor
References
[Use of demeclotetracycline in the treatment of hyponatremia in cirrhotic ascitis]. [2013]The activity of demeclotetracyclin, and ADH antagonist, is studied in 11 ethylic patients with cirrhosis of the liver, under a large hydric diet (1500 cm3). The prescription of the cyclin (600 mg daily) is always determined by a fall of the urinary osmolarity (-36%) and by a dramatic improvement of the free water clearance (+ 60%); consecutively, we observe an increase of natremia in 8 out of 9 cases. Associated with Spironolactone (200 mg daily) the anti-ADH activity persists (the free water clearance becomes positive in 5 out of 10 patients), in spite of the natriuretic activity of anti-aldosterone ; a minimal fall of the natremia is observed in only 2 cases. The indication of Demeclotetracyclin in the curative or preventive treatment of the hyponatremia of the liver cirrhosis is discussed.
Circulatory abnormalities in cirrhosis with focus on neurohumoral aspects. [2022]Patients with cirrhosis exhibit characteristic hemodynamic changes with a hyperkinetic circulation and an abnormal distribution of the blood volume and neurohumoral regulation. Their plasma and noncentral blood volumes are increased, and the central and arterial blood volume and systemic vascular resistance are decreased. A peripheral arterial vasodilatation may be of pathogenic importance to the low systemic vascular resistance as it directly correlates to the degree of central hypovolemia. It may therefore be an important element in the development of the low arterial blood pressure and hyperkinetic circulation in cirrhosis. Various vasodilators such as atrial natriurectic peptide, calcitonin gene-related peptide, adrenomedullin, and nitric oxide are among potential candidates in the arterial vasodilatation in cirrhosis. Besides enhanced sympathetic nervous activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopressin, endothelin-1 may also be implicated in the hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general circulatory dysfunction influencing the course of the disease.
Baseline Severity and Inflammation Would Influence the Effect of Simvastatin on Clinical Outcomes in Cirrhosis Patients. [2023]Simvastatin administration to decompensated cirrhosis patients improved Child-Pugh (CP) at the end of a safety trial (EST).
Effects of atorvastatin on portal hemodynamics and clinical outcomes in patients with cirrhosis with portal hypertension: a proof-of-concept study. [2018]Statins can modulate portal microvascular dynamics in patients with cirrhosis. We present data from a proof-of-concept study aimed at comparing combination of propranolol and atorvastatin versus propranolol alone in reducing portal pressure in patients with cirrhosis.
[Effect of an anabolic steroid (methenolone enanthate) on the intra- and extravasal albumin pool in liver cirrhosis]. [2013]15 patients with a histologically and/or peritoneoscopically proven cirrhosis of the liver were treated for four weeks with 200 mg metenolonenanthate (Depot-Primobolan) per week. Before and after the treatment the intravascular and extravascular pool and daily turnover of albumin were measured with 125J-albumin. All patients had a well "compensated" cirrhosis. The only significant difference between the values of the cirrhotic patients and those of a control group of patients was a reduction of the albumin turn-over. The anabolic steroid enlarged the turn-over, the effect was the more pronounced the more pronounced the more the turn over was diminished before the treatment.
Alcohol and marrow granulocyte reserve response to etiocholanolone. [2013]Measurement of the size of marrow granulocyte reserve (MGR) was performed in ten alcoholic patients with clinically uncomplicated Laennec's cirrhosis and in ten healthy subjects by etiocholanolone injection before and during oral 95% ethyl alcohol administration (30 to 60 ml in orange juice every 6 hours for 48 hours). No significant differences in bone marrow response to etiocholanolone were found between normal subjects studied before and during alcohol administration. The group of cirrhotic patients failed to demonstrate a reduction of MGR when compared to control subjects and alcohol administration did not result in an abnormal response to etiocholanolone. It is suggested that the MGR is normal in most alcoholic patients with clinically uncomplicated Laennec's cirrhosis and is not influenced by acute alcohol ingestion. These results are in contrast to other previous reports in which bacterial endotoxin was used to estimate granulocyte reserve.
[The characteristics of the new indices of hemogram under liver cirrhosis]. [2019]The diagnostic significance of new indices of hemogram under liver cirrhosis associated with thrombocytopenia (n=64) was analyzed. It is established that in comparison with control group the patients with cirrhosis are characterized by statistically valuable increasing of content of immature cells of three germs of hematopoiesis: reticulocytes up to 1.99±1.54%, granulocytes up to 0.44±0.77%, immature thrombocytes up to 3.23±1.7%. Under liver pathology, the following occurrences are detected: "left shift" of reticulocyte and leukocyte formula; reliable decreasing of content of hemoglobin in reticulocytes. The increasing of both of content of fragmentary erythrocytes (Frg) up to 0.83±1.21% and level of delta-hemoglobin (D-He>4 ng) were interpreted as additional markers of hemolysis. At that, negative values of delta-hemoglobin (D-He
Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation. [2019]Thrombocytopenia in cirrhotic patients may be due to deficient production of thrombopoietin.
Early cirrhosis and a preserved bone marrow niche favour regenerative response to growth factors in decompensated cirrhosis. [2020]Exogenous growth factor-mobilized bone marrow (BM) stem cells have shown a differential response in the management of decompensated cirrhosis (DC). This study was designed to evaluate potential clinical benefit of adding Erythropoietin (EPO) in granulocyte-colony stimulating factor (G-CSF)-mobilized stem cell therapy, possible mechanisms of regeneration and predictive factors of regenerative response.
Reduced expression of thrombopoietin is involved in thrombocytopenia in human and rat liver cirrhosis. [2019]It is widely accepted that thrombocytopenia associated with liver cirrhosis is caused by increased platelet destruction in the enlarged spleen, but this issue has not yet been analysed sufficiently in terms of platelet production. Thrombopoietin is produced mainly in the liver and strongly promotes platelet production. We studied serum thrombopoietin and the levels of its mRNA in liver tissue of cirrhotic patients and also in a rat model of liver cirrhosis. Furthermore, to clarify the influence of the spleen, we investigated thrombopoietin mRNA in splenectomized rats. The serum thrombopoietin level in humans with liver cirrhosis was not significantly reduced instead of thrombocytopenia. The expression of thrombopoietin mRNA in liver tissue decreased with the progression of liver cirrhosis in both patients and the rat model and no compensatory expression was observed in other organs or non-parenchymal cells. The level of thrombopoietin mRNA did not differ significantly in splenectomized cirrhotic rats before or after administration of dimethylnitrosamine, but was lower than that in splenectomized rats without cirrhosis. We conclude that thrombocytopenia in liver cirrhosis is caused not only by platelet destruction but also by decreased platelet production, perhaps due to reduction of thrombopoietin mRNA in the liver.