Trial Outcomes & Findings for Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency (NCT NCT01379469)
NCT ID: NCT01379469
Last Updated: 2021-10-12
Results Overview
The effect of Carbamazepine on hepatic ATZ load will be measured by the number of hepatocytes with PAS+/diastase-resistant globules and/or steady state levels of ATZ by immunoblot analysis.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
52 weeks
Results posted on
2021-10-12
Participant Flow
Participant milestones
| Measure |
Drug-Carbamazepine (Tegretol XR)
One arm receives Drug-Carbamazepine (Tegretol XR).All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Drug-Carbamazepine (Tegretol XR): To reduce the likelihood of hypersensitivity reactions the subjects will be started on 400 mg/day in 2 doses and the dose will be increased weekly by 200mg/day until reaching a stable therapeutic concentration with a dose not exceeding 1200mg/day(or 1000mg/day in subjects less than 15 years of age). The CBZ tablets will be encapsulated.
|
Drug-Carbamazepine (Tegretol XR) Placebo
One arm receives Carbamazepine (Tegretol-XR) placebo.All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Carbamazepine (Tegretol XR) Placebo: Carbamazepine (Tegretol XR)Placebo-the subjects will be started on 400mg/day in 2 doses and the dose will be increased weekly by 200 mg/day until reaching a dose not exceeding 1200 mg/day (or 1000 mg/day in subjects less than 15 years of age). The placebo group will receive encapsulated tables without Carbamazepine.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
7
|
|
Overall Study
COMPLETED
|
1
|
3
|
|
Overall Study
NOT COMPLETED
|
12
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency
Baseline characteristics by cohort
| Measure |
Drug-Carbamazepine (Tegretol XR)
n=13 Participants
One arm receives Drug-Carbamazepine (Tegretol XR).All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Drug-Carbamazepine (Tegretol XR): To reduce the likelihood of hypersensitivity reactions the subjects will be started on 400 mg/day in 2 doses and the dose will be increased weekly by 200mg/day until reaching a stable therapeutic concentration with a dose not exceeding 1200mg/day(or 1000mg/day in subjects less than 15 years of age). The CBZ tablets will be encapsulated, and the placebo group will receive encapsulated tablets without CBZ.
|
Drug-Carbamazepine (Tegretol XR) Placebo
n=7 Participants
One arm receives Carbamazepine (Tegretol-XR) placebo.All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Carbamazepine (Tegretol XR) Placebo: Carbamazepine (Tegretol XR)Placebo-the subjects will be started on 400mg/day in 2 doses and the dose will be increased weekly by 200 mg/day until reaching a dose not exceeding 1200 mg/day (or 1000 mg/day in subjects less than 15 years of age). The placebo group will receive encapsulated tables without Carbamazepine.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Age, Continuous
|
50.7 years
STANDARD_DEVIATION 9.4 • n=93 Participants
|
53.7 years
STANDARD_DEVIATION 19.6 • n=4 Participants
|
51.75 years
STANDARD_DEVIATION 13.38 • n=27 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=93 Participants
|
7 participants
n=4 Participants
|
20 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: The primary outcome was not assessable because the number of subjects with available pre \& post PAS+/diastase stained liver biopsies \& tissue for immunoblot was insufficient in subject number and sample quality. To elaborate only 3 subjects had both pre \& post biopsies stained for PAS, 2 from the placebo \& 1 from the Carbamazepine arms \& the available histology quality was insufficient for histomorphormetry. Frozen liver samples were also of insufficient number \& mass for immunoblot.
The effect of Carbamazepine on hepatic ATZ load will be measured by the number of hepatocytes with PAS+/diastase-resistant globules and/or steady state levels of ATZ by immunoblot analysis.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 52 weeksPopulation: The secondary outcome was also not assessable because the number of subjects with available pre \& post trichrome stained liver biopsies \& tissue for hydroxyproline was also insufficient in subject number and sample quality. Again only 3 subjects had both pre \& post biopsies stained for trichrome, 2 placebo- \& 1 Carbamazepine treated. Available histology quality was also insufficient here for histomorphormetry \&.frozen liver samples insufficient for hydroxyproline determination.
For the secondary outcomes we will determine the effect of Carbamazepine treatment on hepatic fibrosis on the basis of sirius red staining and hydroxyproline concentration and whether Carbamazepine treatment changes portal pressure as determined by Hepatic Venous Pressure Gradient.
Outcome measures
Outcome data not reported
Adverse Events
Drug-Carbamazepine (Tegretol XR)
Serious events: 6 serious events
Other events: 13 other events
Deaths: 0 deaths
Drug-Carbamazepine (Tegretol XR) Placebo
Serious events: 4 serious events
Other events: 7 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Drug-Carbamazepine (Tegretol XR)
n=13 participants at risk
One arm receives Drug-Carbamazepine (Tegretol XR).All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Drug-Carbamazepine (Tegretol XR): To reduce the likelihood of hypersensitivity reactions the subjects will be started on 400 mg/day in 2 doses and the dose will be increased weekly by 200mg/day until reaching a stable therapeutic concentration with a dose not exceeding 1200mg/day(or 1000mg/day in subjects less than 15 years of age). The CBZ tablets will be encapsulated, and the placebo group will receive encapsulated tablets without CBZ.
|
Drug-Carbamazepine (Tegretol XR) Placebo
n=7 participants at risk
One arm receives Carbamazepine (Tegretol-XR) placebo.All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Carbamazepine (Tegretol XR) Placebo: Carbamazepine (Tegretol XR)Placebo-the subjects will be started on 400mg/day in 2 doses and the dose will be increased weekly by 200 mg/day until reaching a dose not exceeding 1200 mg/day (or 1000 mg/day in subjects less than 15 years of age). The placebo group will receive encapsulated tables without Carbamazepine.
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal
|
15.4%
2/13 • Number of events 3 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
28.6%
2/7 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
General disorders
Pain
|
15.4%
2/13 • Number of events 3 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
14.3%
1/7 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary
|
7.7%
1/13 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
14.3%
1/7 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Cardiac disorders
Cardiac
|
7.7%
1/13 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
14.3%
1/7 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Infections and infestations
Infection
|
15.4%
2/13 • Number of events 4 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
28.6%
2/7 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Vascular disorders
Vascular
|
15.4%
2/13 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
0.00%
0/7 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
General disorders
Constitutional
|
30.8%
4/13 • Number of events 6 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
0.00%
0/7 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Blood and lymphatic system disorders
Hematologic
|
7.7%
1/13 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
0.00%
0/7 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Metabolism and nutrition disorders
Metabolic/Laboratory
|
7.7%
1/13 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
0.00%
0/7 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
Other adverse events
| Measure |
Drug-Carbamazepine (Tegretol XR)
n=13 participants at risk
One arm receives Drug-Carbamazepine (Tegretol XR).All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Drug-Carbamazepine (Tegretol XR): To reduce the likelihood of hypersensitivity reactions the subjects will be started on 400 mg/day in 2 doses and the dose will be increased weekly by 200mg/day until reaching a stable therapeutic concentration with a dose not exceeding 1200mg/day(or 1000mg/day in subjects less than 15 years of age). The CBZ tablets will be encapsulated, and the placebo group will receive encapsulated tablets without CBZ.
|
Drug-Carbamazepine (Tegretol XR) Placebo
n=7 participants at risk
One arm receives Carbamazepine (Tegretol-XR) placebo.All subjects have severe liver disease due to alpha-1-antitrypsin deficiency.
Carbamazepine (Tegretol XR) Placebo: Carbamazepine (Tegretol XR)Placebo-the subjects will be started on 400mg/day in 2 doses and the dose will be increased weekly by 200 mg/day until reaching a dose not exceeding 1200 mg/day (or 1000 mg/day in subjects less than 15 years of age). The placebo group will receive encapsulated tables without Carbamazepine.
|
|---|---|---|
|
Cardiac disorders
Cardiac
|
7.7%
1/13 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
42.9%
3/7 • Number of events 4 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Hepatobiliary disorders
Child-Pugh Score Increase
|
7.7%
1/13 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
14.3%
1/7 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
General disorders
Constitutional
|
92.3%
12/13 • Number of events 63 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
100.0%
7/7 • Number of events 17 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Skin and subcutaneous tissue disorders
Dermatologic
|
15.4%
2/13 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
28.6%
2/7 • Number of events 4 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Endocrine disorders
Endocrine
|
23.1%
3/13 • Number of events 3 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
14.3%
1/7 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Gastrointestinal disorders
Gastrointestinal
|
69.2%
9/13 • Number of events 35 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
71.4%
5/7 • Number of events 13 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Renal and urinary disorders
Genitourological
|
23.1%
3/13 • Number of events 3 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
28.6%
2/7 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Reproductive system and breast disorders
Gynecological
|
15.4%
2/13 • Number of events 2 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
14.3%
1/7 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Blood and lymphatic system disorders
Hematologic
|
23.1%
3/13 • Number of events 4 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
14.3%
1/7 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Infections and infestations
Infection
|
53.8%
7/13 • Number of events 16 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
42.9%
3/7 • Number of events 5 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Metabolism and nutrition disorders
Metabolic/Laboratory
|
23.1%
3/13 • Number of events 3 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
28.6%
2/7 • Number of events 3 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
53.8%
7/13 • Number of events 12 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
42.9%
3/7 • Number of events 5 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Nervous system disorders
Neurologic
|
76.9%
10/13 • Number of events 31 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
42.9%
3/7 • Number of events 5 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
General disorders
Pain
|
61.5%
8/13 • Number of events 15 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
71.4%
5/7 • Number of events 8 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary
|
30.8%
4/13 • Number of events 9 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
57.1%
4/7 • Number of events 5 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
|
Vascular disorders
Vascular
|
38.5%
5/13 • Number of events 5 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
14.3%
1/7 • Number of events 1 • Serious Adverse Events and Adverse Events were collected for 52 weeks.
|
Additional Information
David Rudnick MD, PhD- Associate Professor
Washington University School of Medicine
Phone: 314-286-2832
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place