Diet, Insulin Sensitivity And the Brain (DISAB)

This study has been completed.
Sponsor:
Collaborator:
Netherlands Organisation for Scientific Research
Information provided by (Responsible Party):
K.E.M. Koopman, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01297738
First received: February 16, 2011
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

Obesity and insulin resistance may be in part explained by an altered reward system with changes in the serotonin/dopamine system. These changes might be caused by changes in dietary habits, especially by an increased intake of liquid sugar and an increase in meal frequency. The investigators hypothesize that increasing meal frequency compared to increasing meal size and when consuming a hypercaloric high-sugar diet (HS) compared to a hypercaloric high-fat-high-sugar diet (HFHS) will result in a reduction in cerebral serotonin and dopamine transporters and in a more prominent increase in insulin resistance. In addition, the investigators hypothesize that the changes in insulin sensitivity will be independent of changes in abdominal (visceral) and liver fat and that changes in insulin sensitivity due to the dietary manipulation will co-occur with changes in insulin signaling pathways in peripheral fat and muscle tissue.


Condition Intervention
Obesity
Diabetes Mellitus Type 2
Other: Meal size increase with HFHS
Other: Meal size increase with HS
Other: Meal frequency increase with HFHS
Other: Meal frequency increase with HS

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Effect of Dietary Patterns and Diet Composition on Insulin Sensitivity and Cerebral Dopamine- and Serotonin Transporters

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Cerebral binding of [123I]FP-CIT to serotonin- and dopamine transporters and correlation with changes in in vivo and ex vivo insulin sensitivity [ Time Frame: At baseline and after 6 weeks of hypercaloric HFHS or HS diet ] [ Designated as safety issue: No ]
    Difference in cerebral binding of the radioligand [123I]FP-CIT to serotonin- and dopamine transporters before and after dietary manipulations and correlation of cerebral dopamine and serotonin transporter binding with changes in in vivo and ex vivo insulin sensitivity.


Secondary Outcome Measures:
  • Abdominal fat mass [ Time Frame: At baseline and after 6 weeks of HFHS or HS hypercaloric diet ] [ Designated as safety issue: No ]
    Changes in accumulated amount of abdominal (visceral) and liver fat

  • Glucoregularoty hormones [ Time Frame: At baseline and after 6 weeks of hypercaloric HFHS- or HS diet ] [ Designated as safety issue: No ]
    Changes in glucoregulatory hormones such as glucagon and leptin

  • Insulin signalling pathways [ Time Frame: At baseline and after 6 weeks of hypercaloric HFHS- or HS diet ] [ Designated as safety issue: No ]
    Changes in insulin signalling pathways in peripheral fat and muscle tissue


Enrollment: 39
Study Start Date: February 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Meal size increase with HFHS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a liquid meal which is high in fat and sugar (Nutridrink®)
Other: Meal size increase with HFHS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a high-fat, high-sugar liquid medical food supplement (Nutridrink®). Subjects consume the Nutridrink® with their meals, which results in an increase in meal size.
Other Name: Nutridrink
Experimental: Meal size increase with HS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume this caloric surplus with their meals, which results in an increase in meal size.
Other: Meal size increase with HS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages with their meals, which results in an increase in meal size.
Experimental: Meal frequency increase with HFHS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a liquid meal which has a high fat and sugar content(Nutridrink®). Subjects consume the Nutridrink 3 times a day in between meals. which results in an increase in meal frequency.
Other: Meal frequency increase with HFHS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a high-fat, high-sugar liquid medical food supplement (Nutridrink®). Subjects consume the Nutridrink® 3 times a day in between meals, which results in an increase in meal frequency.
Other Name: Nutridrink
Experimental: Meal frequency increase with HS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages 3 times a day in between meals, which results in an increase in meal frequency.
Other: Meal frequency increase with HS
On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages 3 times a day in between meals, which results in an increase in meal frequency.
No Intervention: Control group
Subjects will not follow any diet but their own ad-libitum, healty diet.

Detailed Description:

Lean, healthy, young men will follow a hypercaloric HF- or HFHS diet for 6 weeks. Before and after the dietary intervention, the investigators will perform a SPECT-scan for serotonin and dopamine transporters with the radioligand [123I]FP-CIT, administered intravenously. The investigators will also perform a structural MRI for localization. Furthermore the investigators will perform a liver MRS and abdominal MRI for liver fat- and abdominal visceral fat measurement. The investigators will also perform a euglycemic, hyperinsulinemic clamp to measure insulin sensitivity and muscle- and fat biopsies to examine changes in insulin signaling pathways and fat metabolism. After the hypercaloric diet subjects will follow a hypocaloric diet until their weight is back to baseline.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • BMI 19-26 kg/m2
  • Age 18-40 years old
  • Male gender
  • Caucasian
  • Stable weight 3 months prior to start study participation

Exclusion Criteria:

  • Abnormal oral glucose tolerance test (OGTT)
  • Lipid disorders, renal disorders, thyroid disorders, elevated liver enzymes
  • Use of medication
  • Use of alcohol > 3/day
  • Use of ecstasy, amphetamines or cocaine
  • Smoking
  • History of eating disorder or psychiatric disorder
  • Any medical condition, intensive sports ( >3 times/week), shift work
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01297738

Locations
Netherlands
Academic Medical Center
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Netherlands Organisation for Scientific Research
Investigators
Study Director: Mireille JM Serlie, Dr Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator: Karin EM Koopman, MD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

No publications provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: K.E.M. Koopman, ms, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01297738     History of Changes
Other Study ID Numbers: DISAB
Study First Received: February 16, 2011
Last Updated: January 23, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
diet manipulation
serotonin
dopamine
insulin sensitivity

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Endocrine System Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Metabolic Diseases
Insulin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014