Contraceptive Hormone and Reward Measurement (CHARM Study)

Sponsor

University of Colorado, Denver (Other)

Overall Status

Recruiting

CT.gov ID

NCT05058872

Collaborator

(none)

Enrollment

Location

Arms

24.2

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Purpose of this study: The purpose of this study is to learn more about how hormonal oral contraceptives affect brain processes and emotional wellbeing.

Procedures: If participants agree to participate, the following will happen:

Eligibility visit (remote screening session)
If participants are eligible to participate in the study, they will be placed in one of two groups. If they are in the first group, they will be asked to take an oral contraception pill ("study drug") every day for 21 days. If they are in the second, they will take a placebo every day for 21 days. A placebo is a pill that looks like medicine but is not real and will have no medical effect on participants. Participants will not get to choose which group they are in, nor will they be told which group they are in.
During the three-week period in which participants will take either the study drug or placebo, they will be asked to complete daily check-in surveys on their computer or mobile device.
Participants will be asked to attend two additional visits over the course of about three weeks. At these visits, participants will be asked to undergo a urine drug screen, a blood draw, and a magnetic resonance imaging (MRI). They will also be asked to complete behavioral questionnaires.

Condition or Disease	Intervention/Treatment	Phase
Oral Hormonal Contraceptive Use Neural Activity Mood Hedonic Function	Drug: Levonorgestrel/ethinyl estradiol Drug: Placebo	Phase 4

Detailed Description

Hypothesis:

The principal investigator hypothesizes that treatment with oral contraceptives, specifically a combination of a synthetic estrogen and progestin, in adult females will result in deficits in reward processing.

Specific Aims:

Subjective ratings of mood and hedonic function. Based on previous evidence, the principal investigator hypothesizes that H1a) treatment with a hormonal oral contraceptive will result in decreased self-reports of sexual function and interest/enjoyment in non-sexual pleasurable activities as measured by the Sexual Function Questionnaire and Dimensional Anhedonia Rating Scale, respectively.
Neural activity in reward processing areas during an incentive delay task. Via functional magnetic resonance imaging, neural activity will be measured during both the anticipation and receipt of a pleasurable image (erotica, pleasant images of the outdoors, and "cute" animals). Activation of nucleus accumbens and ventromedial pre-frontal cortex is positively associated with feelings of anticipation and pleasure, respectively (10). The principal investigator hypothesizes that H2) treatment with a hormonal oral contraceptive will result in decreased activity in these regions, consistent with decreased reward anticipation and responsiveness.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

Official Title:

Contraceptive Hormone and Reward Measurement (CHARM Study)

Actual Study Start Date :

Sep 20, 2021

Anticipated Primary Completion Date :

Sep 27, 2023

Anticipated Study Completion Date :

Sep 27, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Levonorgestrel/ethinyl estradiol Levonorgestrel 0.15mg/ethinyl estradiol 0.03mg - once a day for 21 days	Drug: Levonorgestrel/ethinyl estradiol Levonorgestrel 0.15mg/ethinyl estradiol 0.03mg
Placebo Comparator: Placebo Placebo once a day for 21 days	Drug: Placebo Placebo comparator

Arm

Intervention/Treatment

Experimental: Levonorgestrel/ethinyl estradiol

Levonorgestrel 0.15mg/ethinyl estradiol 0.03mg - once a day for 21 days

Drug: Levonorgestrel/ethinyl estradiol

Levonorgestrel 0.15mg/ethinyl estradiol 0.03mg

Placebo Comparator: Placebo

Placebo once a day for 21 days

Drug: Placebo

Placebo comparator

Outcome Measures

Primary Outcome Measures

Change in ratings of anhedonia after 21 days of receiving either levonorgestrel/ethinyl estradiol or placebo as measured by the Dimensional Anhedonia Rating Scale [Baseline, 21 days post-intervention]
The Dimensional Anhedonia Rating Scale is validated measure of anhedonia (lack of pleasure, desire, and motivation). Scores range from 17 to 85 with higher scores reflecting a better outcome/less anhedonia
Change in ratings of sexual function after 21 days of receiving either levonorgestrel/ethinyl estradiol or placebo as measured by the Female Sexual Function Index. [Baseline, 21 days post-intervention]
The Female Sexual Function Index is a validated questionnaire of various domains of sexual functioning in women. Scores range from 2 to 36, with higher scores reflecting better outcomes/better sexual function.
Change in Blood Oxygen Level Dependent (BOLD) Signal after 21 days of treatment with either levonorgestrel/ethinyl estradiol or placebo [Baseline, 21 days post-intervention]
Blood-oxygen-level dependent contrast imaging, or BOLD-contrast imaging, is a method used in functional magnetic resonance imaging (fMRI) to observe different areas of the brain or other organs, which are found to be active at any given time. BOLD signal in the brain will be measured during a reward task both at baseline and after 21 days of receiving either levonorgestrel/ethinyl estradiol or placebo.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Aged 18 and older;
Right-handed;
Assigned female at birth;
Regular 21-35 day menstrual cycles for the past 6 months per self-report;
In generally good health per self-report. Those with a chronic medical condition may participate at the discretion of the principal investigator if the condition is stable;
Willingness to abstain from intercourse or use a non-hormonal back-up method of contraception (e.g., condoms) during the entire course of the study;
Negative urine drug screen, excepting marijuana or benzodiazepine that is being prescribed by a physician as a sleep aid, assessed at the baseline visit;
Ability to abstain from caffeine and/or cannabis for 2 hours prior to functional Magnetic Resonance Imaging (fMRI) scan visits;
Access to a reliable internet connection or cell phone data to complete daily questionnaires;
For those wishing to complete study screening session remotely: access to a reliable internet connection, computer to complete electronic consent and a private space to complete the session.

Exclusion Criteria:

Presence or history of severe or unstable physical, neurological (per health history interview) or psychiatric disorders (assessed by Miniature International Neuropsychiatric Interview (MINI) but per Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-V) criteria, and the discretion of the principal investigator);
Lifetime history of psychotic disorders;
History of substance use disorder that has not been in remission (as defined by a substance free period of at least one year). However, individuals with mild disorders, disorders solely limited to cannabis, and/or those who have achieved close to one year of remission may be eligible at the discretion of the PI;
Presence or history of any category 3 or 4 conditions or medications per the CDC's (Centers for Disease Control and Prevention) Medical Eligibility Criteria for Contraceptive Use pertaining to combined hormonal contraceptive methods as per self-report and reviewed by the principal investigator;
Irregular menstrual periods per self-report;
Any current tobacco smoking (former smokers are eligible so long as their quit date was greater than one year ago);
Any personal or family history of a venous thromboembolism;
Known diagnosis of hypertensive disorder;
Any current or past history of malignancy;
Migraines with aura;
Systolic blood pressure greater than or equal to 140 or diastolic pressure greater than or equal to 90 taken at baseline visit;
Currently nursing an infant;
Known chromosomal or hormonal disorder affecting sex steroids;
Use of hormonal contraceptives currently or in the past 3 months, or use of medications that directly affect sex hormones (i.e. gonadotropin releasing hormone agonists, selective estrogen receptor modifiers);
Current pregnancy or pregnancy/delivery in the past six months;
Intention to become pregnant during study participation;
Current use of psychotropic medication;
Claustrophobia;
Metal in body unsafe for magnetic resonance imaging;
Weight over 300 pounds;
Conditions that would make magnetic resonance imaging unsafe for participants (i.e. aneurysm clip, cardiac pacemaker, etc.).