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Behavioral and Neural Phenotypes of Primary Dysmenorrhea in Adolescents

Primary Purpose

Primary Dysmenorrhea

Status

Active

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Quantitative Sensory Testing

fMRI

About this trial

This is an interventional other trial for Primary Dysmenorrhea

Eligibility Criteria

13 Years - 19 Years (Child, Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

Female aged 13-19 years
Self-reported menstrual cycle averaging 22-35 days
Regular menstrual cycles for at least 6 months
Access to a smartphone or email
Right handed
Body Mass Index (BMI) of 35 or less
Able to read and understand English
Ability and willingness to provide written informed assent/consent
Availability of a parent to provide written parental permission (for participants under age 18)

Exclusion Criteria:

Use of oral contraceptives or any exogenous hormones in the previous 3 months prior to participation
Presence of factors indicative of secondary dysmenorrhea (e.g., self-reported presence of persistent pelvic pain throughout the month)
Diagnosis of chronic pain condition (e.g., Irritable bowel syndrome (IBS), functional abdominal pain, interstitial cystitis/painful bladder syndrome)
Current self-reported severe depression, bipolar disorder, panic disorder, or ADHD, or current treatment for these conditions
Diagnosis of an eating disorder within the last 6 months
Current or past diagnosis of any psychotic disorder
Currently pregnant
Self-reported weekly use of alcohol, cannabis, and/or other illegal substances
Use of stimulants (including methamphetamine and/or medications for the treatment of ADHD) or opioids in the previous 3 months. Participants who use other analgesics will be included but will be requested to not take these analgesics within the previous 24 hours of the laboratory session
History of pelvic inflammatory disease or sexually transmitted disease
Acute illness or injury that would potentially impact pain task performance (e.g., fever, flu symptoms) or that affect sensitivity of the extremities (e.g., Reynaud's disease). Potential participants who are being treated for cardiovascular disease(s) will be included pending discussion with the participant's primary physician
Developmental delay, diagnosis of autism, or significant cognitive impairment that may preclude understanding of study procedures
Presence of certain ferromagnetic appliance or implants (braces, retainers, spacers, wires, screws, etc.) in the mouth or any other body part that may be a contraindication for the magnetic resonance imaging (MRI) scanner
Significant fear of enclosed places (claustrophobia)

Sites / Locations

McLean Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

fMRI and laboratory pain induction

Arm Description

Outcomes

Primary Outcome Measures

Menstrual pain

Rating of average pain during the first two days of the most recent menstrual period on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.

Change in menstrual pain from baseline to 12-months post baseline

Change in the rating of average pain during the first two days of the most recent menstrual period on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.

Change in bodily pain from baseline to 12-months post baseline

Change in the number of bodily locations endorsed as painful during the prior month.

Pressure pain sensitivity (PPS)

The pain rating [on a 0 (no pain) to 100 (worst pain possible) numeric rating scale] of a 5-second, 2.0 kg/cm2 application of pressure to the right thumbnail bed.

Pressure pain tolerance (PPT)

The last rated pressure delivered in a series of increasing pressure applications to the right thumbnail bed. Each application of pressure lasts for 5 seconds. The pressure sequence is terminated when the participant reaches their individual tolerance and decides to stop, when the participant reaches the safety maximum amount of pressure, or when the participant rates the pressure >=80 on a 0 (no pain) to 100 (worst pain possible) numeric rating scale.

Trapezius pressure pain threshold (TPPTh)

The amount of pressure, applied by a pressure algometer to the participant's trapezius muscle, needed for the pressure stimulus to first feel painful to the participant.

Conditioned pain modulation (CPM)

Conditioned pain modulation (CPM) assesses pain inhibition. CPM is calculated as the change in the TPPTh between when the pressure is applied by itself (test stimulus) and when it is applied while the participant's hand is submerged in cold water (conditioning stimulus).

Gray matter volume

Gray matter regional volume and surface area will be measured from images obtained during the fMRI session.

White matter fiber tract values

Obtained from fiber tracking using images obtained during diffusion tensor imaging (DTI). Values represent anatomical connectivity of cortical and subcortical brain regions.

Resting state networks

Calculated from images obtained during resting state fMRI. Region-to-region connectivity indices are obtained by correlating fMRI time series corrected for physiological noise and motion. Region-to-region connectivity strength of the regions of interest (i.e., salience, sensorimotor, emotional arousal, and default mode networks) will be assessed for each participant.

Secondary Outcome Measures

Change in menstrual pain from 12-months post baseline to 24-months post baseline

Change in the rating of average pain during the first two days of the most recent menstrual period on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.

Change in bodily pain from 12-months post baseline to 24-months post baseline

Change in the number of bodily locations endorsed as painful during the prior month.

Salivary pro-inflammatory cytokines

Assessment of pro-inflammatory cytokines found in the saliva (e.g., IL-1 Beta, IL-6, IL-8, TNF-Alpha)

Trapezius pressure pain threshold (TPPTh)

The amount of pressure, applied by a pressure algometer to the participant's trapezius muscle, needed for the pressure stimulus to first feel painful to the participant.

Change in conditioned pain modulation (CPM) from baseline to 12-months post baseline

Alterations in pain inhibition will be assessed via the direction of the change (i.e., improvement in pain inhibition, worsening of pain inhibition, and stable pain inhibition) as well as the magnitude of the change.

Change in pressure pain sensitivity (PPS) from baseline to 12-months post baseline

Change in the pain rating [on a 0 (no pain) to 100 (worst pain possible) numeric rating scale] of a 5-second, 2.0 kg/cm2 application of pressure to the right thumbnail bed.

Change in pressure pain tolerance (PPT) from baseline to 12-months post baseline

Change in the PPT described above between baseline and 12-months post baseline.

Change in gray matter volume from baseline to 12-months post baseline

Change in the gray matter regional volume and surface area obtained from images obtained during the fMRI session.

Change in white matter fiber tract values from baseline to 12-months post baseline

Change in the DTI-produced fiber tracking values, which represent anatomical connectivity of cortical and subcortical brain regions.

Change in resting state networks

Change in region-to-region connectivity strength of the regions of interest (i.e., salience, sensorimotor, emotional arousal, and default mode networks).

Full Information

NCT ID

NCT04685343

First Posted

December 2, 2020

Last Updated

October 23, 2023

Sponsor

Mclean Hospital

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

1. Study Identification

Unique Protocol Identification Number

NCT04685343

Brief Title

Behavioral and Neural Phenotypes of Primary Dysmenorrhea in Adolescents

Official Title

Behavioral and Neural Phenotypes of Primary Dysmenorrhea in Adolescents

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 14, 2020 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mclean Hospital

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The study will use primary dysmenorrhea (PD; menstrual pain without an identified organic cause) as a model to examine biomarkers associated with menstrual and non-menstrual bodily pain in adolescent girls, ages 13-19. Participants will undergo extensive phenotyping including pain inhibition testing and multimodal neuroimaging to obtain indices brain structure and function at baseline and 12 months later. Menstrual pain severity and non-menstrual bodily pain will be assessed monthly for 24 months. Aims of the study are: 1) to identify the central mechanisms of PD using measures of pain inhibition and brain structure and connectivity of sensorimotor, default, emotional arousal, and salience networks, 2) to determine deficits in pain inhibition and alterations in brain structure and network connectivity that predict the one-year developmental trajectories of menstrual pain and non-menstrual bodily pain, and 3) to identify the dynamic relationship between alterations in pain inhibition and brain structure and connectivity with symptom change in menstrual pain and non-menstrual bodily pain. We hypothesize that deficits in endogenous pain inhibition and alterations in brain structure, connectivity, and function of regional networks will be positively associated with menstrual pain severity ratings at baseline and predict the trajectory of menstrual and non-menstrual bodily pain over 2 years. The results are expected to identify specific mechanisms and characteristics that predict the transition from acute/cyclical pain to persistent or chronic pain, which will support the development of therapies to prevent the transition from recurrent to chronic pain in adulthood.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Dysmenorrhea

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

164 (Actual)

8. Arms, Groups, and Interventions

Arm Title

fMRI and laboratory pain induction

Arm Type

Experimental

Intervention Type

Behavioral

Intervention Name(s)

Quantitative Sensory Testing

Intervention Description

Quantitative sensory testing (QST) consisting of 4 pain induction and sensory sensitivity tasks (i.e., pressure applied to the thumbnail, arms, shoulders, and lower abdomen, a cold water task, and one video-watching task).

Intervention Type

Other

Intervention Name(s)

fMRI

Intervention Description

Functional magnetic resonance imaging (fMRI) session consisting of structural and functional brain scans.

Primary Outcome Measure Information:

Title

Menstrual pain

Description

Rating of average pain during the first two days of the most recent menstrual period on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.

Time Frame

Baseline

Title

Change in menstrual pain from baseline to 12-months post baseline

Description

Change in the rating of average pain during the first two days of the most recent menstrual period on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.

Time Frame

At baseline and 12 months after baseline

Title

Change in bodily pain from baseline to 12-months post baseline

Description

Change in the number of bodily locations endorsed as painful during the prior month.

Time Frame

At baseline and 12 months after baseline

Title

Pressure pain sensitivity (PPS)

Description

The pain rating [on a 0 (no pain) to 100 (worst pain possible) numeric rating scale] of a 5-second, 2.0 kg/cm2 application of pressure to the right thumbnail bed.

Time Frame

At baseline

Title

Pressure pain tolerance (PPT)

Description

Time Frame

At baseline

Title

Trapezius pressure pain threshold (TPPTh)

Description

The amount of pressure, applied by a pressure algometer to the participant's trapezius muscle, needed for the pressure stimulus to first feel painful to the participant.

Time Frame

At baseline

Title

Conditioned pain modulation (CPM)

Description

Time Frame

At baseline

Title

Gray matter volume

Description

Gray matter regional volume and surface area will be measured from images obtained during the fMRI session.

Time Frame

At baseline

Title

White matter fiber tract values

Description

Obtained from fiber tracking using images obtained during diffusion tensor imaging (DTI). Values represent anatomical connectivity of cortical and subcortical brain regions.

Time Frame

At baseline

Title

Resting state networks

Description

Time Frame

At baseline

Secondary Outcome Measure Information:

Title

Change in menstrual pain from 12-months post baseline to 24-months post baseline

Description

Change in the rating of average pain during the first two days of the most recent menstrual period on a 0 (no pain) to 10 (worst pain possible) numeric rating scale.

Time Frame

12 months after baseline and 24 months after baseline

Title

Change in bodily pain from 12-months post baseline to 24-months post baseline

Description

Change in the number of bodily locations endorsed as painful during the prior month.

Time Frame

12 months after baseline and 24 months after baseline

Title

Salivary pro-inflammatory cytokines

Description

Assessment of pro-inflammatory cytokines found in the saliva (e.g., IL-1 Beta, IL-6, IL-8, TNF-Alpha)

Time Frame

Three time points during each of two study visits: during questionnaire completion (approx. 20 min. after arrival), immediately after the imaging session (approx. 90 min. after arrival), and following the final pain task (approx. 120 min after arrival)

Title

Trapezius pressure pain threshold (TPPTh)

Description

The amount of pressure, applied by a pressure algometer to the participant's trapezius muscle, needed for the pressure stimulus to first feel painful to the participant.

Time Frame

12 months after baseline

Title

Change in conditioned pain modulation (CPM) from baseline to 12-months post baseline

Description

Time Frame

At baseline and 12 months after baseline

Title

Change in pressure pain sensitivity (PPS) from baseline to 12-months post baseline

Description

Change in the pain rating [on a 0 (no pain) to 100 (worst pain possible) numeric rating scale] of a 5-second, 2.0 kg/cm2 application of pressure to the right thumbnail bed.

Time Frame

At baseline and 12 months after baseline

Title

Change in pressure pain tolerance (PPT) from baseline to 12-months post baseline

Description

Change in the PPT described above between baseline and 12-months post baseline.

Time Frame

At baseline and 12 months after baseline

Title

Change in gray matter volume from baseline to 12-months post baseline

Description

Change in the gray matter regional volume and surface area obtained from images obtained during the fMRI session.

Time Frame

At baseline and 12 months after baseline

Title

Change in white matter fiber tract values from baseline to 12-months post baseline

Description

Change in the DTI-produced fiber tracking values, which represent anatomical connectivity of cortical and subcortical brain regions.

Time Frame

At baseline and 12 months after baseline

Title

Change in resting state networks

Description

Change in region-to-region connectivity strength of the regions of interest (i.e., salience, sensorimotor, emotional arousal, and default mode networks).

Time Frame

At baseline and 12 months after baseline

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

13 Years

Maximum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Female aged 13-19 years Self-reported menstrual cycle averaging 22-35 days Regular menstrual cycles for at least 6 months Access to a smartphone or email Right handed Body Mass Index (BMI) of 35 or less Able to read and understand English Ability and willingness to provide written informed assent/consent Availability of a parent to provide written parental permission (for participants under age 18) Exclusion Criteria: Use of oral contraceptives or any exogenous hormones in the previous 3 months prior to participation Presence of factors indicative of secondary dysmenorrhea (e.g., self-reported presence of persistent pelvic pain throughout the month) Diagnosis of chronic pain condition (e.g., Irritable bowel syndrome (IBS), functional abdominal pain, interstitial cystitis/painful bladder syndrome) Current self-reported severe depression, bipolar disorder, panic disorder, or ADHD, or current treatment for these conditions Diagnosis of an eating disorder within the last 6 months Current or past diagnosis of any psychotic disorder Currently pregnant Self-reported weekly use of alcohol, cannabis, and/or other illegal substances Use of stimulants (including methamphetamine and/or medications for the treatment of ADHD) or opioids in the previous 3 months. Participants who use other analgesics will be included but will be requested to not take these analgesics within the previous 24 hours of the laboratory session History of pelvic inflammatory disease or sexually transmitted disease Acute illness or injury that would potentially impact pain task performance (e.g., fever, flu symptoms) or that affect sensitivity of the extremities (e.g., Reynaud's disease). Potential participants who are being treated for cardiovascular disease(s) will be included pending discussion with the participant's primary physician Developmental delay, diagnosis of autism, or significant cognitive impairment that may preclude understanding of study procedures Presence of certain ferromagnetic appliance or implants (braces, retainers, spacers, wires, screws, etc.) in the mouth or any other body part that may be a contraindication for the magnetic resonance imaging (MRI) scanner Significant fear of enclosed places (claustrophobia)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laura Payne, PhD

Organizational Affiliation

Mclean Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

McLean Hospital

City

Belmont

State/Province

Massachusetts

ZIP/Postal Code

02478

Country

United States

12. IPD Sharing Statement

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Behavioral and Neural Phenotypes of Primary Dysmenorrhea in Adolescents

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