Differential Responses to Drugs and Sweet Tastes (HAP)

• ClinicalTrials.gov Identifier: NCT03810703
• Recruitment Status: Completed
• First Posted: January 22, 2019
• Last Update Posted: January 22, 2019
• Sponsor: University of Chicago
• Information provided by (Responsible Party): University of Chicago

Tracking Information

• First Submitted Date: August 1, 2017
• First Posted Date: January 22, 2019
• Last Update Posted Date: January 22, 2019
• Actual Study Start Date: February 9, 2017
• Actual Primary Completion Date: August 9, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 17, 2019)

Addiction Research Center Inventory (ARCI-A) [ Time Frame: End of study (Baseline - time 0 and approximately 4 weeks later) ]

The ARCI is a 49-item true-false scale that assesses participant sensitivity to several drug effect categories including: Amphetamine-like effects scale (e.g., increased energy, sense of well being), Benzedrine-like effects (e.g., increased energy, intellectual productivity), Morphine-Benzedrine-like effects (e.g., pleasant somatic experiences, euphoria), Lysergic Acid Diethylamide-like effects (e.g., dysphoria, somatic discomfort), and Pentobarbital-Chlorpromazine-Alcohol-like effects (e.g., sedation, psychomotor retardation). The primary measure in this study was the peak session rating on the Amphetamine Effects sub-scale

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Differential Responses to Drugs and Sweet Tastes
• Official Title: Hypomania, Amphetamine, and Preferences for Sweets
• Brief Summary: Young adults who exhibit "bipolar phenotype" (BPP), defined as occasional episodes of mood elevation and heightened activity, are at risk for several psychiatric disorders, including problem use of drugs and alcohol. Mood elevation has been linked to higher alcohol consumption and alcohol use disorders. Individuals with BPP show elevated lifetime prevalence of alcohol use disorders (between 39%-61%), figures that exceed those reported in both major depression and schizophrenia. Recently, the investigators demonstrated in a controlled laboratory study that individuals with BPP (but not meeting criteria for full Bipolar I Disorder), report dampened responses to a single dose of alcohol, compared to placebo. In the current study, the investigators seek to extend these findings to determine if young adults reporting BPP, based on a questionnaire, will exhibit reduced responses to other rewarding stimuli, such as d-amphetamine and sweet tastes. The investigators hypothesize that the BPP individuals will exhibit dampened subjective responses to stimulant and sweet taste rewards compared to healthy controls.
• Detailed Description: This study will extend the understanding of risk factors for drug or alcohol misuse, or other reward-related behaviors. The investigators previously showed that individuals who report occasional feelings of high energy and excitability experience less effect from a single dose of alcohol, compared to people who have not experienced these effects. Now the investigators wish to determine if this dampened response also occurs with other rewards, namely feelings of wellbeing after a dose of amphetamine, or liking of a sweet solution. Individuals who exhibit the BPP (i.e., periods of excitability) also are more likely to develop alcohol problems, substance misuse, and weight gain and obesity. Therefore, the investigators will test the working hypothesis that young adults who report having these experiences, based on a questionnaire measure (i.e., BPP individuals) will show dampened subjective responses to both single oral doses of amphetamine or sweet palatable tastes. The investigators will also obtain objective measures (e.g. Respiratory Sinus Arrhythmia and heart rate) to amphetamine and sweet taste, to establish whether the dampened subjective response extends to physiological indices as well. This study will extend the previous literature regarding the blunted effects of alcohol in BPP individuals and will suggest possible mechanisms that promote broader addictive behaviors in individuals with mood disturbance. Importantly, the investigators are proposing to test individuals at a relatively young age, 18-19 years. This is important to identify a risk factor, that is thought to pre-date use of drugs. In older participants, it would be difficult to separate the role of the pre-existing trait from the effect of habitual drug or alcohol use that escalates markedly after age 20.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Study will track participants in two assigned groups (participants that exhibit either High or Low Bipolar II/Hypomanic phenotypes)

Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science

• Condition: Bipolar II Disorder

Intervention

• Drug: Placebo oral capsule
  Placebo oral capsule
• Drug: d-amphetamine 10 mg oral capsule
  d-amphetamine 10 mg oral capsule
• Drug: d-amphetamine 20 mg oral capsule
  d-amphetamine 20 mg oral capsule

Study Arms

• Placebo Comparator: placebo arm
  Participant will receive placebo oral capsule during this four hour session.
  Intervention: Drug: Placebo oral capsule
• Experimental: amphetamine 10 mg arm
  Participant will receive d-amphetamine 10 mg oral capsule during this four hour session.
  Intervention: Drug: d-amphetamine 10 mg oral capsule
• Experimental: amphetamine 20 mg arm
  Participant will receive d-amphetamine 20 mg oral capsule during this four hour session.
  Intervention: Drug: d-amphetamine 20 mg oral capsule

Publications *

• Calabrese JR, Hirschfeld RM, Reed M, Davies MA, Frye MA, Keck PE, Lewis L, McElroy SL, McNulty JP, Wagner KD. Impact of bipolar disorder on a U.S. community sample. J Clin Psychiatry. 2003 Apr;64(4):425-32.
• Chandler RA, Wang PW, Ketter TA, Goodwin GM. A new US-UK diagnostic project: mood elevation and depression in first-year undergraduates at Oxford and Stanford universities. Acta Psychiatr Scand. 2008 Jul;118(1):81-5.
• de Lauzon B, Romon M, Deschamps V, Lafay L, Borys JM, Karlsson J, Ducimetière P, Charles MA; Fleurbaix Laventie Ville Sante Study Group. The Three-Factor Eating Questionnaire-R18 is able to distinguish among different eating patterns in a general population. J Nutr. 2004 Sep;134(9):2372-80.
• Francis LJ, Robbins M, Louden SH, Haley JM. A revised psychoticism scale for the revised Eysenck personality questionnaire: a study among clergy. Psychol Rep. 2001 Jun;88(3 Pt 2):1131-4.
• Williams JB, Gibbon M, First MB, Spitzer RL, Davies M, Borus J, Howes MJ, Kane J, Pope HG Jr, Rounsaville B, et al. The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability. Arch Gen Psychiatry. 1992 Aug;49(8):630-6.
• Grossman P, Taylor EW. Toward understanding respiratory sinus arrhythmia: relations to cardiac vagal tone, evolution and biobehavioral functions. Biol Psychol. 2007 Feb;74(2):263-85. Epub 2006 Nov 1. Review.
• Grossman P, van Beek J, Wientjes C. A comparison of three quantification methods for estimation of respiratory sinus arrhythmia. Psychophysiology. 1990 Nov;27(6):702-14.
• Haertzen CA. Development of scales based on patterns of drug effects, using the addiction Research Center Inventory (ARCI). Psychol Rep. 1966 Feb;18(1):163-94.
• Hoeppner BB, Stout RL, Jackson KM, Barnett NP. How good is fine-grained Timeline Follow-back data? Comparing 30-day TLFB and repeated 7-day TLFB alcohol consumption reports on the person and daily level. Addict Behav. 2010 Dec;35(12):1138-43. doi: 10.1016/j.addbeh.2010.08.013. Epub 2010 Aug 13.
• Hirschfeld RM, Holzer C, Calabrese JR, Weissman M, Reed M, Davies M, Frye MA, Keck P, McElroy S, Lewis L, Tierce J, Wagner KD, Hazard E. Validity of the mood disorder questionnaire: a general population study. Am J Psychiatry. 2003 Jan;160(1):178-80.
• Waleeprakhon P, Ittasakul P, Lotrakul M, Wisajun P, Jullagate S, Ketter TA. Development and validation of a screening instrument for bipolar spectrum disorder: The Mood Disorder Questionnaire Thai version. Neuropsychiatr Dis Treat. 2014 Aug 18;10:1497-502. doi: 10.2147/NDT.S67842. eCollection 2014.
• Jacob T, Seilhamer RA, Bargeil K, Howell DN. Reliability of Lifetime Drinking History among alcohol dependent men. Psychol Addict Behav. 2006 Sep;20(3):333-7.
• Johanson CE, Uhlenhuth EH. Drug preference and mood in humans: d-amphetamine. Psychopharmacology (Berl). 1980;71(3):275-9.
• Kessler RC, Crum RM, Warner LA, Nelson CB, Schulenberg J, Anthony JC. Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry. 1997 Apr;54(4):313-21.
• Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990 Nov 21;264(19):2511-8.
• Rock PL, Goodwin GM, Harmer CJ. The common adolescent bipolar phenotype shows positive biases in emotional processing. Bipolar Disord. 2010 Sep;12(6):606-15. doi: 10.1111/j.1399-5618.2010.00859.x.
• Trost S, Diekhof EK, Mohr H, Vieker H, Krämer B, Wolf C, Keil M, Dechent P, Binder EB, Gruber O. Investigating the Impact of a Genome-Wide Supported Bipolar Risk Variant of MAD1L1 on the Human Reward System. Neuropsychopharmacology. 2016 Oct;41(11):2679-87. doi: 10.1038/npp.2016.70. Epub 2016 May 13.
• Weafer J, Burkhardt A, de Wit H. Sweet taste liking is associated with impulsive behaviors in humans. Front Behav Neurosci. 2014 Jun 17;8:228. doi: 10.3389/fnbeh.2014.00228. eCollection 2014.
• Gontkovsky ST. Sensitivity of the Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-II) to the neurocognitive deficits associated with the semantic dementia variant of frontotemporal lobar degeneration: A case study. Appl Neuropsychol Adult. 2017 May-Jun;24(3):288-293. doi: 10.1080/23279095.2016.1154857. Epub 2016 Apr 21.
• White TL, Justice AJ, de Wit H. Differential subjective effects of D-amphetamine by gender, hormone levels and menstrual cycle phase. Pharmacol Biochem Behav. 2002 Nov;73(4):729-41.
• Yip SW, Doherty J, Wakeley J, Saunders K, Tzagarakis C, de Wit H, Goodwin GM, Rogers RD. Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype. Neuropsychopharmacology. 2012 Jul;37(8):1808-15. doi: 10.1038/npp.2012.45. Epub 2012 Apr 11.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 17, 2019): 41
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 9, 2018
• Actual Primary Completion Date: August 9, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged 18-19 years old
• BMI of 19-26
• Physical/EKG/Medical History/Medications Approved by Physician for d-amphetamine
• at least High School education
• Fluent in English

Exclusion Criteria:

• No Current Mood, Anxiety, Eating or Psychotic Disorder
• No current psychotropic medication
• No Recent Drug Dependence
• < 4 alcoholic drinks/day for males; < 3 alcoholic drinks/day for females (monthly average)
• No weekly (or more frequent) illicit drug use
• No women who are pregnant, nursing, or planning pregnancy within 3 months (birth control is okay)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 19 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03810703
• Other Study ID Numbers: IRB16-1293
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Chicago
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Chicago
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Chicago
• Verification Date: August 2017