Familial Partial LipodystrophyPhase 2NCT02430077
Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients
A Phase 2 study testing Obeticholic Acid in people with Familial Partial Lipodystrophy, run by Abhimanyu Garg at 2 sites in United States.
Trial summary
Lipodystrophies are rare disorders characterized by selective loss of adipose tissue and predisposition to insulin resistance and its metabolic complications. Hepatic steatosis is a common complication in patients with partial and generalized lipodystrophies.Despite aggressive management of diabetes and… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Familial Partial Lipodystrophy
- What is being tested?
- Obeticholic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2016to Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with familial partial lipodystrophy of the Dunnigan variety with heterozygous disease-causing missense mutation in lamin A/C (LMNA) gene.
- Hepatic steatosis (>5.6% hepatic triglyceride content) as demonstrated by 1H magnetic resonance spectroscopy.
- Age 18-70 years.
- Alcohol intake of less than 20 g per day in females and 30 g per day in males.
- Participants and their partners with whom they are having sex, must use medically-acceptable birth control (contraceptives) during the study. Medically-acceptable methods of contraception include: (1) surgical sterilization, such as hysterectomy, tubal ligation or vasectomy. (2) approved hormonal contraceptives, such as birth control pills, patch or ring; Depo-Provera, Implanon. (3) barrier methods, such as condom, cervical cap or diaphragm used with a spermicide. (4) an intrauterine device (IUD).
Who cannot join
- Laboratory or other histologic findings highly suggestive of liver disease due to causes other than non-alcoholic steatohepatitis, such as chronic viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, biliary obstruction or genetic liver diseases such as Wilson's disease, hemochromatosis or alpha-1-antitrypsin deficiency.
- Treatment with drugs associated with steatohepatitis, e.g., corticosteroids, high dose estrogens, methotrexate, amiodarone, tamoxifen, valproic acid, sulfasalazine, or oxacillin for more than 2 weeks in the 6 months prior to the study.
- Decompensated liver disease as evidenced by clinical features of hepatic failure (variceal bleeding, ascites, hepatic encephalopathy etc.) and laboratory investigations (prolonged prothrombin time with INR > 1.3, hypoalbuminemia with serum albumin less than 3.0 g/dL, direct bilirubin > 1.3 mg/dL, or presence of esophageal varices etc.)
- Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study suggestive of liver cancer.
- Use of drugs which can potentially decrease hepatic steatosis during previous 3 months; ursodeoxycholic acid, thiazolidinediones, high-dose vitamin E, betaine, acetylcysteine and choline.
- Significant systemic or major illnesses other than liver disease, such as congestive heart failure, cerebrovascular disease, respiratory failure, renal failure (serum creatinine >2 mg/dL), acute pancreatitis, organ transplantation, serious psychiatric disease, and malignancy, that could interfere with the trial and adequate follow up.
Show all 15Show fewer
- Acute medical illnesses precluding participation in the studies.
- Known HIV-infected patient.
- Current substance abuse.
- Pregnant or lactating woman.
- Hematocrit of less than 30%.
- History of weight loss during past 3 months.
- Patients on bile acid binding resins, cholestyramine, colestipol or colesevelam.
- Hypersensitivity or intolerance to OCA or any components of its formulation.
- Failure to give informed consent 16 .Previous clinical diagnosis of diabetes mellitus or fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
UT Southwestern Medical Center 5323 Harry Hines Blvd
Dallas, Texas, 75390-8537
UT Southwestern Medical Center
Dallas, Texas, 75390
About this study
Lipodystrophies are rare disorders characterized by selective loss of adipose tissue and predisposition to insulin resistance and its metabolic complications. Hepatic steatosis is a common complication in patients with partial and generalized lipodystrophies.Despite aggressive management of diabetes and hyperlipidemia, hepatic steatosis and its complications present a therapeutic challenge in many patients. Due to this large disease burden, it is important to assess the efficacy and safety of novel therapies for hepatic steatosis in patients with lipodystrophies.There are, however, no systematic studies evaluating various therapeutic interventions for reducing hepatic steatosis in patients with lipodystrophies. A variety of drugs have been investigated in nonlipodystrophic patients with non-alcoholic hepatic steatosis and steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD). Recent data support the activation of the farnesoid X receptor (FXR, NR1H4), a nuclear hormone receptor regulated by bile acids, for treatment of NASH and NAFLD. FXR activates transcription of several genes particularly the atypical nuclear receptor small heterodimer partner (SHP, NR0B2) and thus can influence triglyceride metabolism within hepatocytes.Both cholic acid (CA) and chenodeoxycholic acid (CDCA) are ligands for FXR, however, UDCA which is the 7 hydroxy β-epimer of CDCA, does not activate FXR. Obeticholic acid (OCA) is a first-in-class selective FXR agonist which has approximately 100 fold greater FXR-agonistic activity in the nanomolar range, as compared to CDCA .It therefore appears that FXR modulation offers interesting therapeutic possibilities in treating hepatic steatosis. This study is primarily designed to study efficacy of OCA, a strong FXR ligand, in reducing hepatic triglyceride levels in patients with hepatic steatosis and Familial Partial Lipodystrophy (FPLD). If proven to be effective, it may reduce morbidity and mortality as a result of sequelae of hepatic steatosis in patients with lipodystrophies.
Read the detailed description
This study will be a randomized, placebo-controlled cross-over trial. Patients who are considered eligible for the study will undergo screening evaluation to determine their eligibility for the trial. For those who are found to be eligible, during the baseline period, they will continue their usual diet and other lifestyle measures without changing any medications for 1 month in order to establish a baseline state. Three blood samples will be obtained during this period at the Clinical and Translational Research Center. Following the baseline period, the patients will receive obeticholic acid (OCA) or an identical placebo in the dose of 25 mg/day for a period of 4 months and then will receive the other treatment (OCA or placebo) for 4 months. There will be a wash-out period of 4 months in-between the two study periods.
Patients will be educated to maintain their usual physical activities and diet during the study. The subjects will be admitted to the Clinical and Translational Research Center for the baseline evaluations (at the beginning of the two study periods), and at the end of four months during each study period.
- Conditions
- Familial Partial Lipodystrophy
- Being tested
- Obeticholic Acid, Placebo
- Keywords
- Hepatic Steatosis
- Medical subject headings
- Lipodystrophy, Familial Partial, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Obeticholic AcidDrug
Also called NEW DRUG APPLICATION
Capsules of obeticholic acid (OCA) or an identical placebo in the dose of 25 mg/day for a period of 4 months .
PlaceboDrug
Also called Identical to Obeticholic Acid placebo drug
Identical to Obeticholic Acid - placebo drug
| Study group | Role | What they receive |
|---|---|---|
| Active capsule of Obeticholic acid | Experimental | Patient will receive obeticholic acid (OCA) in the dose of 25 mg/day for a period of 4 months. Receives: Drug: Obeticholic Acid |
| Pacebo for Obeticholic acid | Placebo comparator | Patient will recieve placebo in the dose of 25 mg/day for a period of 4 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Liver Triglycerides (TG).
The primary end-point variable was the change in the liver TG content assessed using proton-density fat fraction mapping by Magnetic Resonance Imaging (MRI).
Measured: Baseline, 4 months
Secondary outcomes (6)
Change in Serum Triglyceride Levels
Change in the serum levels of Triglycerides from baseline to month 4 is being assessed.
Measured: Baseline, Month 4
Change in Serum Levels of Alanine Aminotransferase
Change in serum levels of Alanine Aminotransferase from baseline to month 4 is assessed
Measured: Baseline, Month 4
Change in Serum Levels of Aspartate Aminotransferases
Change in serum levels of Aspartate Aminotransferases from baseline to month 4 is assessed
Measured: Baseline, Month4
Change in Serum Levels of Gamma-Glutamyl Transpeptidase
Change in serum levels of Gamma-Glutamyl Transpeptidase from baseline to month 4 is assessed
Measured: Baseline, Month 4
Changes in Serum Insulin Levels
Changes in serum Insulin levels is assessed
Measured: Baseline, Month 4
Change in Hepatic Insulin Sensitivity
Change in hepatic insulin sensitivity is assessed by suppression of hepatic glucose output during the low-dose and high-dose insulin infusions during the euglycemic clamp study.
Measured: Baseline, Month 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2015 (estimated)
- Study startJun 2016
- Primary completionOct 2022
- Study completionDec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Familial Partial LipodystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abhimanyu Garg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Abhimanyu Garg, University of Texas Southwestern Medical Center
- Investigators
- Abhimanyu Garg, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02430077
- Sponsor's protocol ID
- STU 062014-033
- Status last verified
- Aug 2024
- First submitted
- 24 Apr 2015
- Last updated
- 27 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients
- ClinicalTrials.gov ID
- NCT02430077
- Acronym / sponsor ID
- STU 062014-033
- Conditions
- Familial Partial Lipodystrophy
- Keywords
- Hepatic Steatosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Abhimanyu GargUniversity, hospital or other
- Study start
- Jun 2016 (actual)
- Primary completion
- Oct 2022 (actual)
- Study completion
- Dec 2022 (actual)
- First posted
- 29 Apr 2015 (estimated)
- Results
- Posted 13 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Lipodystrophies are rare disorders characterized by selective loss of adipose tissue and predisposition to insulin resistance and its metabolic complications. Hepatic steatosis is a common complication in patients with partial and generalized lipodystrophies.Despite aggressive management of diabetes and hyperlipidemia, hepatic steatosis and its complications present a therapeutic challenge in many patients. Due to this large disease burden, it is important to assess the efficacy and safety of novel therapies for hepatic steatosis in patients with lipodystrophies.There are, however, no systematic studies evaluating various therapeutic interventions for reducing hepatic steatosis in patients with lipodystrophies. A variety of drugs have been investigated in nonlipodystrophic patients with non-alcoholic hepatic steatosis and steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD). Recent data support the activation of the farnesoid X receptor (FXR, NR1H4), a nuclear hormone receptor regulated by bile acids, for treatment of NASH and NAFLD. FXR activates transcription of several genes particularly the atypical nuclear receptor small heterodimer partner (SHP, NR0B2) and thus can influence triglyceride metabolism within hepatocytes.Both cholic acid (CA) and chenodeoxycholic acid (CDCA) are ligands for FXR, however, UDCA which is the 7 hydroxy β-epimer of CDCA, does not activate FXR. Obeticholic acid (OCA) is a first-in-class selective FXR agonist which has approximately 100 fold greater FXR-agonistic activity in the nanomolar range, as compared to CDCA .It therefore appears that FXR modulation offers interesting therapeutic possibilities in treating hepatic steatosis. This study is primarily designed to study efficacy of OCA, a strong FXR ligand, in reducing hepatic triglyceride levels in patients with hepatic steatosis and Familial Partial Lipodystrophy (FPLD). If proven to be effective, it may reduce morbidity and mortality as a result of sequelae of hepatic steatosis in patients with lipodystrophies.
Detailed description
This study will be a randomized, placebo-controlled cross-over trial. Patients who are considered eligible for the study will undergo screening evaluation to determine their eligibility for the trial. For those who are found to be eligible, during the baseline period, they will continue their usual diet and other lifestyle measures without changing any medications for 1 month in order to establish a baseline state. Three blood samples will be obtained during this period at the Clinical and Translational Research Center. Following the baseline period, the patients will receive obeticholic acid (OCA) or an identical placebo in the dose of 25 mg/day for a period of 4 months and then will receive the other treatment (OCA or placebo) for 4 months. There will be a wash-out period of 4 months in-between the two study periods.
Patients will be educated to maintain their usual physical activities and diet during the study. The subjects will be admitted to the Clinical and Translational Research Center for the baseline evaluations (at the beginning of the two study periods), and at the end of four months during each study period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active capsule of Obeticholic acid | Experimental | Drug: Obeticholic AcidPatient will receive obeticholic acid (OCA) in the dose of 25 mg/day for a period of 4 months. |
| Pacebo for Obeticholic acid | Placebo comparator | Drug: PlaceboPatient will recieve placebo in the dose of 25 mg/day for a period of 4 months. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with familial partial lipodystrophy of the Dunnigan variety with heterozygous disease-causing missense mutation in lamin A/C (LMNA) gene.
- Hepatic steatosis (>5.6% hepatic triglyceride content) as demonstrated by 1H magnetic resonance spectroscopy.
- Age 18-70 years.
- Alcohol intake of less than 20 g per day in females and 30 g per day in males.
- Participants and their partners with whom they are having sex, must use medically-acceptable birth control (contraceptives) during the study. Medically-acceptable methods of contraception include: (1) surgical sterilization, such as hysterectomy, tubal ligation or vasectomy. (2) approved hormonal contraceptives, such as birth control pills, patch or ring; Depo-Provera, Implanon. (3) barrier methods, such as condom, cervical cap or diaphragm used with a spermicide. (4) an intrauterine device (IUD).
Key exclusion criteria (15 listed)
- Laboratory or other histologic findings highly suggestive of liver disease due to causes other than non-alcoholic steatohepatitis, such as chronic viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, biliary obstruction or genetic liver diseases such as Wilson's disease, hemochromatosis or alpha-1-antitrypsin deficiency.
- Treatment with drugs associated with steatohepatitis, e.g., corticosteroids, high dose estrogens, methotrexate, amiodarone, tamoxifen, valproic acid, sulfasalazine, or oxacillin for more than 2 weeks in the 6 months prior to the study.
- Decompensated liver disease as evidenced by clinical features of hepatic failure (variceal bleeding, ascites, hepatic encephalopathy etc.) and laboratory investigations (prolonged prothrombin time with INR > 1.3, hypoalbuminemia with serum albumin less than 3.0 g/dL, direct bilirubin > 1.3 mg/dL, or presence of esophageal varices etc.)
- Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study suggestive of liver cancer.
- Use of drugs which can potentially decrease hepatic steatosis during previous 3 months; ursodeoxycholic acid, thiazolidinediones, high-dose vitamin E, betaine, acetylcysteine and choline.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Obeticholic AcidAlso: NEW DRUG APPLICATIONCapsules of obeticholic acid (OCA) or an identical placebo in the dose of 25 mg/day for a period of 4 months . | Drug | Active capsule of Obeticholic acid |
| PlaceboAlso: Identical to Obeticholic Acid placebo drugIdentical to Obeticholic Acid - placebo drug | Drug | Pacebo for Obeticholic acid |
Primary outcome
Change in the Liver Triglycerides (TG).
Time frame: Baseline, 4 months
The primary end-point variable was the change in the liver TG content assessed using proton-density fat fraction mapping by Magnetic Resonance Imaging (MRI).
6 secondary outcomes
Change in Serum Triglyceride Levels
Time frame: Baseline, Month 4
Change in Serum Levels of Alanine Aminotransferase
Time frame: Baseline, Month 4
Change in Serum Levels of Aspartate Aminotransferases
Time frame: Baseline, Month4
Change in Serum Levels of Gamma-Glutamyl Transpeptidase
Time frame: Baseline, Month 4
Changes in Serum Insulin Levels
Time frame: Baseline, Month 4
Change in Hepatic Insulin Sensitivity
Time frame: Baseline, Month 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abhimanyu Garg, MD principal investigator
University of Texas Southwestern Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Obeticholic Acid in people with Familial Partial Lipodystrophy, run by Abhimanyu Garg at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Liver Triglycerides (TG). (time frame: Baseline, 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2024.