Trial record 9 of 455 for:    "lipid metabolism, inborn errors" OR "farber lipogranulomatosis"

Measure Liver Fat Content After ISIS 301012 (Mipomersen) Administration

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00362180
First received: August 7, 2006
Last updated: September 19, 2012
Last verified: September 2012
  Purpose

This study will assess what, if any, effect that ISIS 301012 (mipomersen) has on liver triglyceride content in multiple groups of subjects with varying degrees of risk for hepatic steatosis. In order to enroll subject groups with varying degrees of risk, the study has included multiple cohorts (Cohorts A-G). Additions and removal of cohorts has been accomplished with protocol amendments.


Condition Intervention Phase
Lipid Metabolism, Inborn Errors
Hyperlipidemias
Metabolic Diseases
Hypolipoproteinemia
Hypolipoproteinemias
Hypobetalipoproteinemias
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Congenital Abnormalities
Metabolic Disorder
Hypercholesterolemia
Dyslipidemias
Lipid Metabolism Disorders
Drug: ISIS 301012 (mipomersen) sodium
Drug: Placebo
Drug: ISIS 301012 (mipomersen) sodium
Drug: placebo
Drug: ISIS 301012 (mipomersen) sodium
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of ApoB Reduction by ISIS 301012 on Liver Triglyceride Content in Subjects With Varying Degrees of Hyperlipidemia

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • Change from baseline in liver triglyceride content as measured by magnetic resonance spectroscopy (MRS) [ Time Frame: Through end of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (apoB) [ Time Frame: Through end of study ] [ Designated as safety issue: No ]
  • Summary of Adverse Events [ Time Frame: Through end of study ] [ Designated as safety issue: Yes ]

Enrollment: 38
Study Start Date: July 2006
Study Completion Date: September 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A (healthy volunteers) - active
Placebo controlled group to measure the effect of ISIS 301012 (mipomersen) treatment on liver triglyceride content in healthy volunteers.
Drug: ISIS 301012 (mipomersen) sodium
6 subcutaneous injections of 200 mg ISIS 301012 (mipomersen) over 22 days.
Other Names:
  • ISIS 301012
  • mipomersen
Placebo Comparator: Group A (healthy volunteers) - placebo
A placebo-controlled group to measure the effect of ISIS 301012 (mipomersen) treatment on liver triglyceride content in healthy volunteers.
Drug: Placebo
6 subcutaneous injections of 200 mg placebo over 22 days.
Experimental: Group D (fasting glucose and mixed dyslipidemia) - active
A placebo-controlled group to measure the effect of ISIS 301012 (mipomersen) treatment on liver triglyceride content in patients with impaired fasting glucose and mixed dyslipidemia.
Drug: ISIS 301012 (mipomersen) sodium
6 subcutaneous injections of 200 mg ISIS 301012 (mipomersen) over 22 days.
Other Names:
  • ISIS 301012
  • mipomersen
Placebo Comparator: Group D (fasting glucose and mixed dyslipidemia) - placebo
A placebo-controlled group to measure the effect of ISIS 301012 (mipomersen) treatment on liver triglyceride content in patients with impaired fasting glucose and mixed dyslipidemia.
Drug: Placebo
6 subcutaneous injections of 200 mg placebo over 22 days.
Experimental: Group E (uncomplicated HeFH) - active
Placebo-controlled group to measure the effect of ISIS 301012 (mipomersen) treatment on liver triglyceride content in patients with uncomplicated heterozygous familial hypercholesterolemia (HeFH).
Drug: ISIS 301012 (mipomersen) sodium
13 subcutaneous injections of 200 mg ISIS 301012 (mipomersen) over 85 days.
Other Names:
  • ISIS 301012
  • mipomersen
Placebo Comparator: Group E (uncomplicated HeFH) - placebo
Placebo-controlled group to measure the effect of ISIS 301012 (mipomersen) treatment on liver triglyceride content in subjects with uncomplicated heterozygous familial hypercholesterolemia (HeFH).
Drug: placebo
13 subcutaneous injections of 200 mg placebo over 85 days.
No Intervention: GroupGroup F (familial hypobetalipoproteinemia (FBHL))
A reference group of subjects with familial hypobetalipoproteinemia (FBHL) to be examined as a reference population for the effects of reduced expression of apolipoprotein B, but will not receive any investigational product.
Experimental: Group G (Type 2 diabetes)- active
A placebo controlled group to measure the effect of ISIS 301012 (mipomersen) on liver triglyceride content in subjects with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels.
Drug: ISIS 301012 (mipomersen) sodium
200 mg / week mipomersen by subcutaneous injection over 52 weeks.
Other Names:
  • ISIS 301012
  • mipomersen
Placebo Comparator: Group G (Type 2 diabetes) - placebo
A placebo controlled group to measure the effect of ISIS 301012 (mipomersen) on liver triglyceride content in subjects with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels.
Drug: placebo
200 mg / week placebo by subcutaneous injection over 28 weeks.

Detailed Description:

Hypercholesterolemia is characterized by markedly elevated low density lipoprotein (LDL).

ISIS 301012 (mipomersen) Mipomersen is an antisense drug that reduces a protein in the liver cells called apolioprotein B-100 (apoB-100). ApoB-100 plays a role in producing low density lipoprotein cholesterol (LDL-C) (the "bad" cholesterol) and moving it from the liver to one's bloodstream. High LDL-C is an independent risk factor for the development of coronary heart disease (CHD) or other diseases of blood vessels. It has been shown that lowering LDL-C reduces the risk of heart attacks and other major adverse cardiovascular events. There is some evidence that low apoB levels are associated with increases in liver triglyceride content.

The purpose of this study will be to further define mechanisms of hepatic homeostasis in the setting of down regulated hepatic triglyceride export secondary to apoB inhibition. Since the clinical assessment of liver triglyceride is insensitive and non-specific, the assessment will be performed via the most sensitive non-invasive measure of hepatic triglyceride content, namely magnetic resonance spectroscopy (MRS). The study will include: healthy subjects, those with heterozygous familial hypercholesterolemia (HeFH), subjects with impaired fasting glucose and mixed dyslipidemia, and type 2 diabetics with hypercholesterolemia. These participants will be randomized to receive either placebo or ISIS 301012 (mipomersen). FHBL subjects will not receive placebo or ISIS 301012 (mipomersen) but will serve as a reference population because they have naturally reduced apoB levels and increased hepatic triglyceride content. MRS will be performed at varying time points depending on the patient population and dosing schedule.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Group A - are healthy subjects
  • Group D - has impaired fasting glucose and mixed dyslipidemia
  • Group E - has a diagnosis of Heterozygous Familial Hypercholesterolemia (HeFH) and on stable lipid-lowering therapy for 3 months
  • Group F - has a diagnosis of Familial Hypobetalipoproteinemia (FHBL)
  • Group G - has a diagnosis of Diabetes and hypercholesterolemia

Exclusion Criteria:

  • Medical, surgical, laboratory or other conditions which in the judgment of the Physician Investigator would make the subject unsuitable for enrollment, or potentially interfere with subject participation or completion of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00362180

Locations
Netherlands
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided by Genzyme, a Sanofi Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00362180     History of Changes
Other Study ID Numbers: 301012-CS10, 2005-005783-90, EudraCT No: 2005-005783-90
Study First Received: August 7, 2006
Last Updated: September 19, 2012
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Genzyme, a Sanofi Company:
LDL-cholesterol
apoB-100
apoB-48
triglyceride
HeFH
FHBL

Additional relevant MeSH terms:
Lipid Metabolism, Inborn Errors
Congenital Abnormalities
Genetic Diseases, Inborn
Hypercholesterolemia
Hyperlipidemias
Hypobetalipoproteinemias
Hypolipoproteinemias
Infant, Newborn, Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Sphingolipidoses
Dyslipidemias
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lipidoses
Lysosomal Storage Diseases
Mipomersen
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Molecular Probes

ClinicalTrials.gov processed this record on August 01, 2014