NCT00943059

Brief Summary

Accumulation of lipid in skeletal and cardiac muscle has been associated with insulin resistance and diabetic cardiomyopathy. In skeletal muscle, lipotoxic damage has been suggested to lead to dysfunction of mitochondria. It remains unknown whether lipotoxicity leads to mitochondrial dysfunction in heart as well, and if so, whether this also leads to cardiomyopathy (failure of the heart). Although it has been shown that lipid lowering agents can improve insulin sensitivity, the effect of lowering free fatty acids on cardiac and skeletal muscle mitochondrial function remains unknown. In this study the investigators want to investigate whether lowering cardiac and muscular lipid content will improve mitochondrial and cellular function in type 2 diabetic patients. To this end, type 2 diabetic patients and body mass index (BMI)-matched controls will be included in a blinded cross-over design, in which subjects will receive a lipid lowering agent (Acipimox) or placebo for 2 weeks in random order. During treatment, diabetes medication will be stopped. Baseline measurements will be performed prior to the study and after each treatment to assess cardiac and muscular lipid accumulation, cardiac function, mitochondrial function and insulin sensitivity.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at below P25 for not_applicable diabetes-mellitus-type-2

Timeline
Completed

Started Mar 2010

Typical duration for not_applicable diabetes-mellitus-type-2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 20, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 21, 2009

Completed
7 months until next milestone

Study Start

First participant enrolled

March 1, 2010

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
Last Updated

May 14, 2013

Status Verified

May 1, 2013

Enrollment Period

2.8 years

First QC Date

July 20, 2009

Last Update Submit

May 13, 2013

Conditions

Diabetes Mellitus, Type 2Cardiomyopathy, Dilated

Keywords

Mitochondrial functionDiabetesCardiomyopathyinsulin resistancelipid loweringtriglyceridesAcipimox

Outcome Measures

Primary Outcomes (3)

  • changes in mitochondrial function

    2 weeks

  • changes in cardiac function

    2 weeks

  • lipid accumulation in ectopic tissue (cardiac and skeletal muscle)

    2 weeks

Secondary Outcomes (2)

  • insulin sensitivity

    2 weeks

  • oxidative stress markers

    2 weeks

Study Arms (2)

Acipimox

EXPERIMENTAL

Subjects will receive Acipimox or a placebo in random order. Acipimox is a commercially available and registrated drug, that lowers free fatty acids by inhibiting hormone sensitive lipase in the peripheral adipose tissue. No serious side-effects are known other than rare anaphylactic reactions.

Drug: Acipimox

Cellulosum mycrocryst capsula

PLACEBO COMPARATOR

Subjects will receive Acipimox or a placebo in random order. Acipimox is a commercially available and registrated drug, that lowers free fatty acids by inhibiting hormone sensitive lipase in the peripheral adipose tissue. No serious side-effects are known other than rare anaphylactic reactions.

Drug: Cellulosum Mycrocryst

Interventions

AcipimoxDRUG

A capsula is given with 250mg Acipimox, 3dd; 1 after each meal. This will be done during 14 days.

Also known as: Olbetam, Nedios
Acipimox
Cellulosum MycrocrystDRUG

Capsule with cellulosum powder; this has to be taken 3 dd; 1 after each meal during 14 days.

Also known as: Placebo
Cellulosum mycrocryst capsula

Eligibility Criteria

Age40 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or postmenopausal females
  • Age 40-70 years
  • Obese (BMI \> 30 kg/m2), non-insulin dependent type 2 diabetic patients and BMI matched control subjects without diabetes.
  • Generally healthy with specifically no known cardiovascular disease, dyslipidemia, or gastric ulcers (contra-ind. of Acipimox), which can affect the study parameters.
  • Must be on sulphonylurea(SU)- derivate or metformin therapy for at least six months with a constant dose for at least two months, or on dietary treatment for at least six months
  • Well-controlled diabetes: HbA1c\<8%.
  • Control subjects must have a plasma glucose lower than 6,1 mmol/L.
  • Stable dietary habits (no weight loss/gain \> 3 kg in the last 6 months)

You may not qualify if:

  • Known cardiovascular disease, dyslipidemia, hepatic or renal failure and gastric ulcers.
  • Insulin dependent Diabetic patients.
  • Use of lipid lowering agents, except from Statins, as these do not affect triglycerides levels (with exception to Lipitor).
  • Use of Thiazolidines (glitazone/rosiglitazone/pioglitazone/troglitazone)
  • Use of anti-coagulants (not thrombocyte-aggregation inhibitors)
  • Aberrant ECG (with signs of ischemia or cardiac failure or arrythmia's)
  • Weight gain/loss \> 3 kg in the last 6 months.
  • Hb \< 7,3 in women, and \< 7,8 in men.
  • Contraindications for MRI scans:
  • Electronic implants such as pacemakers or neurostimulator
  • Iron-containing corpora aliena in eyes or brain
  • Some hearing aids and artificial (heart) valves which are contraindicated for MRS
  • Claustrophobia
  • Subjects, who do not want to be informed about unexpected medical findings, or do not wish that their physician is informed, cannot participate in the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Maastricht University Medical Centre

Maastricht, 6200MD, Netherlands

Location

Related Publications (6)

  • Schrauwen-Hinderling VB, Kooi ME, Hesselink MK, Jeneson JA, Backes WH, van Echteld CJ, van Engelshoven JM, Mensink M, Schrauwen P. Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects. Diabetologia. 2007 Jan;50(1):113-20. doi: 10.1007/s00125-006-0475-1. Epub 2006 Nov 9.

    PMID: 17093944BACKGROUND

  • Phielix E, Schrauwen-Hinderling VB, Mensink M, Lenaers E, Meex R, Hoeks J, Kooi ME, Moonen-Kornips E, Sels JP, Hesselink MK, Schrauwen P. Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients. Diabetes. 2008 Nov;57(11):2943-9. doi: 10.2337/db08-0391. Epub 2008 Aug 4.

    PMID: 18678616BACKGROUND

  • De Feyter HM, Lenaers E, Houten SM, Schrauwen P, Hesselink MK, Wanders RJ, Nicolay K, Prompers JJ. Increased intramyocellular lipid content but normal skeletal muscle mitochondrial oxidative capacity throughout the pathogenesis of type 2 diabetes. FASEB J. 2008 Nov;22(11):3947-55. doi: 10.1096/fj.08-112318. Epub 2008 Jul 24.

    PMID: 18653763BACKGROUND

  • Schrauwen-Hinderling VB, Roden M, Kooi ME, Hesselink MK, Schrauwen P. Muscular mitochondrial dysfunction and type 2 diabetes mellitus. Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):698-703. doi: 10.1097/MCO.0b013e3282f0eca9.

    PMID: 18089950BACKGROUND

  • Houzelle A, Jorgensen JA, Schaart G, Daemen S, van Polanen N, Fealy CE, Hesselink MKC, Schrauwen P, Hoeks J. Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity. Diabetologia. 2021 Feb;64(2):424-436. doi: 10.1007/s00125-020-05335-w. Epub 2020 Nov 30.

    PMID: 33258025DERIVED

  • Phielix E, Jelenik T, Nowotny P, Szendroedi J, Roden M. Reduction of non-esterified fatty acids improves insulin sensitivity and lowers oxidative stress, but fails to restore oxidative capacity in type 2 diabetes: a randomised clinical trial. Diabetologia. 2014 Mar;57(3):572-81. doi: 10.1007/s00125-013-3127-2. Epub 2013 Dec 6.

    PMID: 24310562DERIVED

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Cardiomyopathy, DilatedDiabetes MellitusCardiomyopathiesInsulin Resistance

Interventions

acipimox

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesCardiomegalyHeart DiseasesCardiovascular DiseasesLaminopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHyperinsulinism

Study Officials

  • Patrick Schrauwen, PhD

    Maastricht University Medical Centre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 20, 2009

First Posted

July 21, 2009

Study Start

March 1, 2010

Primary Completion

December 1, 2012

Study Completion

December 1, 2012

Last Updated

May 14, 2013

Record last verified: 2013-05

Locations

NL(1)