Smoking, Sex Hormones, and Pregnancy

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01811225
• Collaborator: (none)
• Enrollment: 95
• Location: 1
• Arms: 2
• Duration (Months): 54
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The investigators aim to (1) examine the association between levels of progesterone (Prog), allopregnanolone (Allo), and the estradiol/progesterone (E2/P) ratios with smoking-related symptomatology during ad libitum smoking and (2) determine the association between Prog, Allo, and E2/P with the changes in smoking-related symptomatology and response to nicotine following overnight abstinence

Condition or Disease	Intervention/Treatment	Phase
Nicotine Dependence; Contraception	Drug: Low-dose Progesterone; Drug: High-dose Progesterone	Phase 2

Detailed Description

The sample population will consist of oral contraceptive users, both "low" and "high" dose levels of exogenous progesterone with a consistent dose of exogenous estrogen. Participants will complete data collection procedures including providing saliva (cortisol to measure stress), urine (cotinine and 3-Hydroxycotinine to measure nicotine exposure), and blood (progesterone, allopregnanolone, and estradiol) samples, as well as ecological momentary assessments (EMA) daily for seven-days. Participants will also complete a 3-hour smoking topography lab session after overnight abstinence and a 4.5-hour nicotine nasal spray lab session after a 14-hour abstinence. These sessions will contain a nicotine challenge via smoking a cigarette or nasal spray with timed-series physiological, subjective, and behavioral responses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Smoking, Sex Hormones, and Pregnancy
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low-Dose Contraceptive, then High-Dose Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given Tri-Sprintec and generic Prometrium. Participants in this arm will begin with the "low" dose progesterone, which is seven days of placebo Tri-sprintec + placebo generic Prometrium twice daily (7AM and 7PM). Then participants in this arm will move to the "high" dose progesterone, which is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice daily (7AM and 7PM).	Drug: Low-dose Progesterone; The "low" progesterone dose is seven days of placebo Tri-sprintec + placebo generic Prometrium twice a day (7AM and 7PM).; Drug: High-dose Progesterone; The "high" progesterone dose is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice a day (7AM and 7PM).
Experimental: High-Dose Contraceptive, then Low-Dose Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given Tri-Sprintec and generic Prometrium. Participants in this arm will begin with the "high" progesterone dose, which is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice daily (7AM and 7PM). Then participants in this arm will move to the "low" dose progesterone, which is seven days of placebo Tri-sprintec + placebo generic Prometrium twice daily (7AM and 7PM).	Drug: Low-dose Progesterone; The "low" progesterone dose is seven days of placebo Tri-sprintec + placebo generic Prometrium twice a day (7AM and 7PM).; Drug: High-dose Progesterone; The "high" progesterone dose is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice a day (7AM and 7PM).

Outcome Measures

Primary Outcome Measures

1. Change in Smoking Urges [after overnight abstinence on day 8]

   Questionnaire on Smoking Urges-Brief (QSU-Brief): This ten-item version of the original form (QSU) was developed by Tiffany and Drobes and has an excellent level of reliability (α = .97). Total QSU-Brief. Scores can average between 1-7. A higher scores means more urges.

Secondary Outcome Measures

1. Change in Positive and Negative Affect Scale Following Overnight Abstinence [after overnight abstinence on day 8]

   Positive and Negative Affect Scale (PANAS): Participants rate 20 words associated with positive or negative affect using a five-point Likert-type scale. This scale has been shown to have high internal consistency. Positive PANAS scores can range from 10-50. A higher score means greater positive affect. Negative PANAS score can range from 10-50. A higher score means greater negative affect.

2. Change in Cohen Perceived Stress Scale [after overnight abstinence on day 8]

   Cohen Perceived Stress Scale (PSS): This ten-item questionnaire has been validated in a variety of populations including pregnant and postpartum women. It uses five-items to assess ten questions resulting in two factors negative feelings and inability to handle stress. It has high internal reliability (alpha = 0.75). Score range from 0-56. A higher score means more perceived stress.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• currently taking oral contraceptives

• English fluency

• Ability to provide informed consent

Exclusion Criteria:

• use of progestin only contraceptive

• pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• University of Minnesota

Investigators

• Principal Investigator: Sharon S. Allen, M.D., Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 2, 2016

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01811225
• Other Study ID Numbers: 2012NTLS018
• First Posted: Mar 14, 2013
• Last Update Posted: Nov 13, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tobacco Use Disorder; Progesterone

Study Results

Participant Flow

Arm/Group Title	Low-Dose Contraceptive, Then High-Dose	High-Dose Contraceptive, Then Low-Dose
Arm/Group Description	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given Tri-Sprintec and generic Prometrium. Participants in this arm will begin with the "low" dose progesterone, which is seven days of placebo Tri-sprintec + placebo generic Prometrium twice daily (7AM and 7PM). Then participants in this arm will move to the "high" dose progesterone, which is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice daily (7AM and 7PM).	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given Tri-Sprintec and generic Prometrium. Participants in this arm will begin with the "high" progesterone dose, which is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice daily (7AM and 7PM). Then participants in this arm will move to the "low" dose progesterone, which is seven days of placebo Tri-sprintec + placebo generic Prometrium twice daily (7AM and 7PM).
Period Title: Treatment Period 1
STARTED	49	46
COMPLETED	24	29
NOT COMPLETED	25	17
Period Title: Treatment Period 1
STARTED	24	29
COMPLETED	20	23
NOT COMPLETED	4	6

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants at baseline
Overall Participants	70
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	70 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	25
Sex: Female, Male (Count of Participants)
Female	70 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black	12 17.1%
White	41 58.6%
Native American	5 7.1%
Asian	2 2.9%
Mixed Race	9 12.9%
Hawaiian/Pacific Islander	1 1.4%
Region of Enrollment (participants) [Number]
United States	70 100%

Outcome Measures

1. Primary Outcome

Title	Change in Smoking Urges
Description	Questionnaire on Smoking Urges-Brief (QSU-Brief): This ten-item version of the original form (QSU) was developed by Tiffany and Drobes and has an excellent level of reliability (α = .97). Total QSU-Brief. Scores can average between 1-7. A higher scores means more urges.
Time Frame	after overnight abstinence on day 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Contraceptive	High-Dose Contraceptive
Arm/Group Description	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given a low-dose contraceptive. The "low" progesterone dose is seven days of placebo Tri-sprintec + placebo generic Prometrium twice a day (7AM and 7PM).	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given a high-dose contraceptive. The "high" progesterone dose is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice a day (7AM and 7PM).
Measure Participants	34	36
Mean (Standard Deviation) [score on a scale]	5.0 (1.4)	5.5 (2.1)

2. Secondary Outcome

Title	Change in Positive and Negative Affect Scale Following Overnight Abstinence
Description	Positive and Negative Affect Scale (PANAS): Participants rate 20 words associated with positive or negative affect using a five-point Likert-type scale. This scale has been shown to have high internal consistency. Positive PANAS scores can range from 10-50. A higher score means greater positive affect. Negative PANAS score can range from 10-50. A higher score means greater negative affect.
Time Frame	after overnight abstinence on day 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Contraceptive	High-Dose Contraceptive
Arm/Group Description	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given a low-dose contraceptive. The "low" progesterone dose is seven days of placebo Tri-sprintec + placebo generic Prometrium twice a day (7AM and 7PM).	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given a high-dose contraceptive. The "high" progesterone dose is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice a day (7AM and 7PM).
Measure Participants	34	36
Positive Affect	26.21	24.09
Negative Affect	17.01	15.41

3. Secondary Outcome

Title	Change in Cohen Perceived Stress Scale
Description	Cohen Perceived Stress Scale (PSS): This ten-item questionnaire has been validated in a variety of populations including pregnant and postpartum women. It uses five-items to assess ten questions resulting in two factors negative feelings and inability to handle stress. It has high internal reliability (alpha = 0.75). Score range from 0-56. A higher score means more perceived stress.
Time Frame	after overnight abstinence on day 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Contraceptive	High-Dose Contraceptive
Arm/Group Description	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given a low-dose contraceptive. The "low" progesterone dose is seven days of placebo Tri-sprintec + placebo generic Prometrium twice a day (7AM and 7PM).	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given a high-dose contraceptive. The "high" progesterone dose is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice a day (7AM and 7PM).
Measure Participants	34	36
Mean (Standard Deviation) [score on a scale]	14 (4.3)	15 (3.8)

Adverse Events

Time Frame	AE were collected from oral contraceptive users over 3 months
Arm/Group Title	Low-Dose Contraceptive		High-Dose Contraceptive
Arm/Group Description	Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given a low-dose contraceptive. The "low" progesterone dose is seven days of placebo Tri-sprintec + placebo generic Prometrium twice a day (7AM and 7PM).		Females, 18-35 years old, non-pregnant, using oral contraceptive for at least the last 3 months before enrollment will be given a high-dose contraceptive. The "high" progesterone dose is seven days of placebo Tri-Sprintec + 200mg of generic Prometrium twice a day (7AM and 7PM).
All Cause Mortality
	Low-Dose Contraceptive		High-Dose Contraceptive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/36 (0%)
Serious Adverse Events
	Low-Dose Contraceptive		High-Dose Contraceptive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Low-Dose Contraceptive		High-Dose Contraceptive
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/34 (55.9%)		17/36 (47.2%)
Gastrointestinal disorders
Diarrhea	2/34 (5.9%)	2	0/36 (0%)	0
General disorders
Breast Tenderness or soreness	2/34 (5.9%)	2	4/36 (11.1%)	4
Fatigue	0/34 (0%)	0	2/36 (5.6%)	2
Dizzy lightheaded	1/34 (2.9%)	1	0/36 (0%)	0
Headache	7/34 (20.6%)	7	5/36 (13.9%)	5
Restless legs	0/34 (0%)	0	1/36 (2.8%)	1
Nausea	0/34 (0%)	0	2/36 (5.6%)	2
Vomiting	1/34 (2.9%)	1	1/36 (2.8%)	1
Infections and infestations
Cold and Sinus infection	3/34 (8.8%)	3	1/36 (2.8%)	1
Pregnancy, puerperium and perinatal conditions
pain	2/34 (5.9%)	2	0/36 (0%)	0
Vomiting	1/34 (2.9%)	1	1/36 (2.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.