ObesityNCT01949636
The Chocolate Study
An observational study of Obesity, run by Oregon Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to test the dynamic vulnerability model of obesity using brain imaging. Read more about this study
- Who is it for?
- Ages 14 to 16 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Functional Magnetic Resonance Imaging
- How many people
- 131 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Apr 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
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 14 to 16 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: 130 lean adolescents between 14-16 years old with BMIs between the 25th and 75th percentile at baseline
Who may be able to join
- between 14-16 years old
- BMI between 25th and 75th percentile
Who cannot join
- contraindicators of functional magnetic resonance imaging (fMRI)
- metal implants
- braces
- pregnancy
- symptoms of major psychiatric disorders (substance use disorders, conduct disorder, attention deficit hyperactive disorder, major depression, bipolar disorder, panic disorder, agoraphobia, generalized anxiety disorder)
- binge eating
Show all 10Show fewer
- use of pyschoactive drugs
- serious medical conditions (diabetes, brain injury)
- smoking
- dietary allergy to dairy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An fMRI Test of the Dynamic Vulnerability Model of Obesity: Risk Factor Plasticity
The purpose of this study is to test the dynamic vulnerability model of obesity using brain imaging.
Read the detailed description
Obese vs lean humans show greater gustatory/oral somatosensory and reward region responsivity to palatable food images/cues and this predicts future weight gain (Yokum et al., 2011; Stice et al., 2008, 2010b; Stoeckel et al., 2008), in line with reward surfeit and incentive sensitization models of obesity (Berridge, 2009; Davis et al., 2004). Yet, obese vs lean humans have fewer dopamine (DA) receptors in striatal reward regions, show reduced striatal response to palatable food intake, and low striatal response predicts future weight gain in those at genetic risk for reduced DA signaling (Felsted et al., 2010; Stice et al., 2008; Wang et al., 2001; Volkow et al., 2008), in line with the reward deficit model of obesity (Wang et al., 2002b). One explanation for the mixed findings is that some of these findings reflect initial risk factors and others result from overeating. Firing of DA neurons in reward regions shifts from food intake to cues that predict food intake after conditioning (Kiyatkin et al., 1994; Schultz et al., 1993) and overeating leads to reduced D2 receptor density, D2 sensitivity, and reward sensitivity in rats (Alsio et al., 2010; Kelley et al., 2003; Johnson \& Kenny, 2010) and striatal response to food in humans (Stice et al., 2010a), implying that overeating leads to increased incentive sensitization and down-regulation of reward regions. Further, reduced inhibitory region response to food images/cues predicts future overeating and weight gain (Cornier et al., 2010). Data imply that youth at risk for obesity initially show greater responsivity of regions that encode the reward value of food cues, coupled with greater responsivity of gustatory/oral somatosensory regions that encode the sugar and fat content of foods, and with reduced inhibitory region responsivity, which lead to overeating/weight gain that produces blunted striatal DA signaling, increased responsivity of reward valuation regions to food cues, and reduced inhibitory activation in response to food stimuli, increasing risk for further overeating/weight gain. We propose to conduct a rigorous test of this dynamic-vulnerability model using a novel repeated measures fMRI design in which teens complete scans annually over 4 years. Aim 1: test whether elevated gustatory/oral somatosensory and reward region responsivity and reduced inhibitory region responsivity to palatable food images, cues, and intake of food varying in sugar/fat content, and behavioral inhibitory control deficits/immediate reward bias predict initial increases in % body fat in 130 lean teens. Aim 2: use growth curve models to test whether initial increases in % body fat and energy dense food intake predict future decreases in striatal response to palatable food receipt, increases in reward circuitry response to palatable food images/cues, decreased inhibitory region response to food images/cues, and increased behavioral inhibitory control deficits/immediate reward bias. Aim 3: test whether decreased striatal response to palatable food, increased reward region response to food images/cues, reduced inhibitory region response to food images/cues, behavioral inhibitory control deficits/immediate reward bias predict further escalation in % body fat.
- Conditions
- Obesity
- Being tested
- Functional Magnetic Resonance Imaging
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Functional Magnetic Resonance ImagingOther
| Study group | Role | What they receive |
|---|---|---|
| lean adolescents | Not described Receives: Other: Functional Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
increases in BMI
Whether increases in BMI are predicted by: elevated reward region responsivity and reduced inhibitory region responsivity to palatable food varying in sugar/fat content (measured during fMRI scan)
Measured: 1, 2, 3, and 4 years
Secondary outcomes (1)
striatal response to palatable food receipt; reward response and inhibitory response to palatable food cues, and inhibitory control deficits/immediate reward bias
whether increases in BMI and food intake predict: decreased striatal response to palatable food receipt, increased reward response and decreased inhibitory response to palatable food cues, and increased inhibitory control deficits/immediate reward bias (as measured during fMRI scan assessment).
Measured: 1, 2, 3, and 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2013 (estimated)
- Study startMay 2012
- Primary completionJun 2016
- Study completionApr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric Stice, Ph.D., Principal investigator, Oregon Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01949636
- Sponsor's protocol ID
- 092468
- Other IDs
- R01DK092468
- Status last verified
- May 2018
- First submitted
- 18 Jul 2013
- Last updated
- 24 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Alsio J, Olszewski PK, Norback AH, Gunnarsson ZE, Levine AS, Pickering C, Schioth HB. Dopamine D1 receptor gene expression decreases in the nucleus accumbens upon long-term exposure to palatable food and differs depending on diet-induced obesity phenotype in rats. Neuroscience. 2010 Dec 15;171(3):779-87. doi: 10.1016/j.neuroscience.2010.09.046. Epub 2010 Sep 26.
PubMed 20875839Berridge KC. 'Liking' and 'wanting' food rewards: brain substrates and roles in eating disorders. Physiol Behav. 2009 Jul 14;97(5):537-50. doi: 10.1016/j.physbeh.2009.02.044. Epub 2009 Mar 29.
PubMed 19336238Cornier MA, Salzberg AK, Endly DC, Bessesen DH, Tregellas JR. Sex-based differences in the behavioral and neuronal responses to food. Physiol Behav. 2010 Mar 30;99(4):538-43. doi: 10.1016/j.physbeh.2010.01.008. Epub 2010 Jan 22.
PubMed 20096712Davis C, Strachan S, Berkson M. Sensitivity to reward: implications for overeating and overweight. Appetite. 2004 Apr;42(2):131-8. doi: 10.1016/j.appet.2003.07.004.
PubMed 15010176Felsted JA, Ren X, Chouinard-Decorte F, Small DM. Genetically determined differences in brain response to a primary food reward. J Neurosci. 2010 Feb 17;30(7):2428-32. doi: 10.1523/JNEUROSCI.5483-09.2010.
PubMed 20164326Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010 May;13(5):635-41. doi: 10.1038/nn.2519. Epub 2010 Mar 28.
PubMed 20348917Kelley AE, Will MJ, Steininger TL, Zhang M, Haber SN. Restricted daily consumption of a highly palatable food (chocolate Ensure(R)) alters striatal enkephalin gene expression. Eur J Neurosci. 2003 Nov;18(9):2592-8. doi: 10.1046/j.1460-9568.2003.02991.x.
PubMed 14622160Kiyatkin EA, Gratton A. Electrochemical monitoring of extracellular dopamine in nucleus accumbens of rats lever-pressing for food. Brain Res. 1994 Aug 1;652(2):225-34. doi: 10.1016/0006-8993(94)90231-3.
PubMed 7953734Schultz W, Apicella P, Ljungberg T. Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J Neurosci. 1993 Mar;13(3):900-13. doi: 10.1523/JNEUROSCI.13-03-00900.1993.
PubMed 8441015Stice E, Davis K, Miller NP, Marti CN. Fasting increases risk for onset of binge eating and bulimic pathology: a 5-year prospective study. J Abnorm Psychol. 2008 Nov;117(4):941-6. doi: 10.1037/a0013644.
PubMed 19025239Stice E, Yokum S, Blum K, Bohon C. Weight gain is associated with reduced striatal response to palatable food. J Neurosci. 2010 Sep 29;30(39):13105-9. doi: 10.1523/JNEUROSCI.2105-10.2010.
PubMed 20881128Stice E, Yokum S, Bohon C, Marti N, Smolen A. Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4. Neuroimage. 2010 May 1;50(4):1618-25. doi: 10.1016/j.neuroimage.2010.01.081. Epub 2010 Jan 29.
PubMed 20116437Stoeckel LE, Weller RE, Cook EW 3rd, Twieg DB, Knowlton RC, Cox JE. Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage. 2008 Jun;41(2):636-47. doi: 10.1016/j.neuroimage.2008.02.031. Epub 2008 Mar 4.
PubMed 18413289Volkow ND, Wang GJ, Telang F, Fowler JS, Thanos PK, Logan J, Alexoff D, Ding YS, Wong C, Ma Y, Pradhan K. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. Neuroimage. 2008 Oct 1;42(4):1537-43. doi: 10.1016/j.neuroimage.2008.06.002. Epub 2008 Jun 13.
PubMed 18598772Wang GJ, Volkow ND, Felder C, Fowler JS, Levy AV, Pappas NR, Wong CT, Zhu W, Netusil N. Enhanced resting activity of the oral somatosensory cortex in obese subjects. Neuroreport. 2002 Jul 2;13(9):1151-5. doi: 10.1097/00001756-200207020-00016.
PubMed 12151759
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An fMRI Test of the Dynamic Vulnerability Model of Obesity: Risk Factor Plasticity
- ClinicalTrials.gov ID
- NCT01949636
- Acronym / sponsor ID
- 092468
- Conditions
- Obesity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Oregon Research InstituteUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- May 2012
- Primary completion
- Jun 2016 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 24 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the dynamic vulnerability model of obesity using brain imaging.
Detailed description
Obese vs lean humans show greater gustatory/oral somatosensory and reward region responsivity to palatable food images/cues and this predicts future weight gain (Yokum et al., 2011; Stice et al., 2008, 2010b; Stoeckel et al., 2008), in line with reward surfeit and incentive sensitization models of obesity (Berridge, 2009; Davis et al., 2004). Yet, obese vs lean humans have fewer dopamine (DA) receptors in striatal reward regions, show reduced striatal response to palatable food intake, and low striatal response predicts future weight gain in those at genetic risk for reduced DA signaling (Felsted et al., 2010; Stice et al., 2008; Wang et al., 2001; Volkow et al., 2008), in line with the reward deficit model of obesity (Wang et al., 2002b). One explanation for the mixed findings is that some of these findings reflect initial risk factors and others result from overeating. Firing of DA neurons in reward regions shifts from food intake to cues that predict food intake after conditioning (Kiyatkin et al., 1994; Schultz et al., 1993) and overeating leads to reduced D2 receptor density, D2 sensitivity, and reward sensitivity in rats (Alsio et al., 2010; Kelley et al., 2003; Johnson \& Kenny, 2010) and striatal response to food in humans (Stice et al., 2010a), implying that overeating leads to increased incentive sensitization and down-regulation of reward regions. Further, reduced inhibitory region response to food images/cues predicts future overeating and weight gain (Cornier et al., 2010). Data imply that youth at risk for obesity initially show greater responsivity of regions that encode the reward value of food cues, coupled with greater responsivity of gustatory/oral somatosensory regions that encode the sugar and fat content of foods, and with reduced inhibitory region responsivity, which lead to overeating/weight gain that produces blunted striatal DA signaling, increased responsivity of reward valuation regions to food cues, and reduced inhibitory activation in response to food stimuli, increasing risk for further overeating/weight gain. We propose to conduct a rigorous test of this dynamic-vulnerability model using a novel repeated measures fMRI design in which teens complete scans annually over 4 years. Aim 1: test whether elevated gustatory/oral somatosensory and reward region responsivity and reduced inhibitory region responsivity to palatable food images, cues, and intake of food varying in sugar/fat content, and behavioral inhibitory control deficits/immediate reward bias predict initial increases in % body fat in 130 lean teens. Aim 2: use growth curve models to test whether initial increases in % body fat and energy dense food intake predict future decreases in striatal response to palatable food receipt, increases in reward circuitry response to palatable food images/cues, decreased inhibitory region response to food images/cues, and increased behavioral inhibitory control deficits/immediate reward bias. Aim 3: test whether decreased striatal response to palatable food, increased reward region response to food images/cues, reduced inhibitory region response to food images/cues, behavioral inhibitory control deficits/immediate reward bias predict further escalation in % body fat.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| lean adolescents | – | Other: Functional Magnetic Resonance Imaging |
Who may qualify
- Ages
- 14 to 16 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- 130 lean adolescents between 14-16 years old with BMIs between the 25th and 75th percentile at baseline
Key inclusion criteria (2 listed)
- between 14-16 years old
- BMI between 25th and 75th percentile
Key exclusion criteria (10 listed)
- contraindicators of functional magnetic resonance imaging (fMRI)
- symptoms of major psychiatric disorders (substance use disorders, conduct disorder, attention deficit hyperactive disorder, major depression, bipolar disorder, panic disorder, agoraphobia, generalized anxiety disorder)
- binge eating
- use of pyschoactive drugs
- serious medical conditions (diabetes, brain injury)
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 |
|---|---|---|
| Functional Magnetic Resonance Imaging | Other | lean adolescents |
Primary outcome
increases in BMI
Time frame: 1, 2, 3, and 4 years
Whether increases in BMI are predicted by: elevated reward region responsivity and reduced inhibitory region responsivity to palatable food varying in sugar/fat content (measured during fMRI scan)
1 secondary outcome
striatal response to palatable food receipt; reward response and inhibitory response to palatable food cues, and inhibitory control deficits/immediate reward bias
Time frame: 1, 2, 3, and 4 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2018.
- Background: PubMed 20875839Alsio J, Olszewski PK, Norback AH, Gunnarsson ZE, Levine AS, Pickering C, Schioth HB. Dopamine D1 receptor gene expression decreases in the nucleus accumbens upon long-term exposure to palatable food and differs depending on diet-induced obesity phenotype in rats. Neuroscience. 2010 Dec 15;171(3):779-87. doi: 10.1016/j.neuroscience.2010.09.046. Epub 2010 Sep 26.
- Background: PubMed 19336238Berridge KC. 'Liking' and 'wanting' food rewards: brain substrates and roles in eating disorders. Physiol Behav. 2009 Jul 14;97(5):537-50. doi: 10.1016/j.physbeh.2009.02.044. Epub 2009 Mar 29.
- Background: PubMed 20096712Cornier MA, Salzberg AK, Endly DC, Bessesen DH, Tregellas JR. Sex-based differences in the behavioral and neuronal responses to food. Physiol Behav. 2010 Mar 30;99(4):538-43. doi: 10.1016/j.physbeh.2010.01.008. Epub 2010 Jan 22.
- Background: PubMed 15010176Davis C, Strachan S, Berkson M. Sensitivity to reward: implications for overeating and overweight. Appetite. 2004 Apr;42(2):131-8. doi: 10.1016/j.appet.2003.07.004.
- Background: PubMed 20164326Felsted JA, Ren X, Chouinard-Decorte F, Small DM. Genetically determined differences in brain response to a primary food reward. J Neurosci. 2010 Feb 17;30(7):2428-32. doi: 10.1523/JNEUROSCI.5483-09.2010.
- Background: PubMed 20348917Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010 May;13(5):635-41. doi: 10.1038/nn.2519. Epub 2010 Mar 28.
- Background: PubMed 14622160Kelley AE, Will MJ, Steininger TL, Zhang M, Haber SN. Restricted daily consumption of a highly palatable food (chocolate Ensure(R)) alters striatal enkephalin gene expression. Eur J Neurosci. 2003 Nov;18(9):2592-8. doi: 10.1046/j.1460-9568.2003.02991.x.
- Background: PubMed 7953734Kiyatkin EA, Gratton A. Electrochemical monitoring of extracellular dopamine in nucleus accumbens of rats lever-pressing for food. Brain Res. 1994 Aug 1;652(2):225-34. doi: 10.1016/0006-8993(94)90231-3.
- Background: PubMed 8441015Schultz W, Apicella P, Ljungberg T. Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J Neurosci. 1993 Mar;13(3):900-13. doi: 10.1523/JNEUROSCI.13-03-00900.1993.
- Background: PubMed 19025239Stice E, Davis K, Miller NP, Marti CN. Fasting increases risk for onset of binge eating and bulimic pathology: a 5-year prospective study. J Abnorm Psychol. 2008 Nov;117(4):941-6. doi: 10.1037/a0013644.
- Background: PubMed 20881128Stice E, Yokum S, Blum K, Bohon C. Weight gain is associated with reduced striatal response to palatable food. J Neurosci. 2010 Sep 29;30(39):13105-9. doi: 10.1523/JNEUROSCI.2105-10.2010.
- Background: PubMed 20116437Stice E, Yokum S, Bohon C, Marti N, Smolen A. Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4. Neuroimage. 2010 May 1;50(4):1618-25. doi: 10.1016/j.neuroimage.2010.01.081. Epub 2010 Jan 29.
- Recruitment websiteLink provided by the sponsor.
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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.
Eric Stice, Ph.D. principal investigator
Oregon Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity, run by Oregon Research Institute at 1 site 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 2 inclusion and 10 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 24 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
increases in BMI (time frame: 1, 2, 3, and 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01949636, which also lists 20 linked publications.
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 24 May 2018.