Clinical trial NCT06798584: How Does Perimenopausal Menorrhagia Affect Women's Quality of Life and Cognitive Function?
Official title: Rough Journey to Menopause: How Does Perimenopausal Menorrhagia Affect Women's Quality of Life and Cognitive Function?
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Iron Deficiency Anemia Treatment
Iron Deficiency
Iron Deficiency (Without Anemia)
Keywords: Iron
Perimenopause
Iron Deficiency Anemia
Iron Deficiency
Cognitive Function
Quality of Life
Mood
Quality of Family Relationships
Menopause
Perimenopausal Menorrhagia
Abnormal Uterine Bleeding
Menopause Transition
Women&#39;s Health
Lead sponsor: Purdue University
Sponsor class: OTHER
First posted: 2025-01-29
Enrollment: 240
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be classified as iron sufficient, iron deficient, or iron deficient anemic according to the following parameters. To be classified as iron deficient anemic (IDA): Hb between 100 and 119 g/L, and at least 2 of the following iron deficiency parameters: mean corpuscular volume (MCV) \< 80 fL, transferrin saturation (TSAT) \<15%, serum ferritin (Ft) \<15 ug/L, serum transferrin receptor \>8.3 mg/L, serum hepcidin \<8 ng/mL; to be classified as iron deficient without anemia (ID): at least 2 of the abnormal values listed above with a Hb\>=120 g/L; to be classified as iron sufficient (IS): Hb \>=120 g/L, MCV \>80 fL, TSAT \>15%, Ft \>20 ug/L, TfR \< 6 mg/L, and hepcidin \>8 ng/mL. Any participant with a Hb \<100 g/L will be excluded from the study as being too anemic and be referred to a physician for immediate treatment of the anemia. Any participant with a Ft\>200 ug/L will be excluded from the study and advised to follow up with a physician.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to investigate how iron status and heavy bleeding during the menopausal transition affect women's cognitive function and quality of life. The main questions it aims to answer are:

* What is the association between iron status, cognitive function, mood, quality of family relationships, and quality of life in perimenopausal women?
* How does iron repletion, via supplementation, affect cognitive function, mood, quality of family relationships, and quality of life in perimenopausal women?

The investigators will compare the effect of iron supplements to a placebo (gelatin capsule) to see if iron supplements could improve iron status, cognitive function, mood, quality of family relationships, and quality of life of iron-deficient and/or anemic women undergoing the menopausal transition.

Each participant will:

* Make 2 visits (about 2 hours each - baseline and endline) to the Clinical Research Center at Purdue
* Make a very brief visit at midpoint (about 10 minutes) for a checkup
* Take a daily study supplement or placebo for 4 months

Detailed description: (i) Recruitment: The investigators will recruit participants through advertisements and referrals. The investigators will utilize advertisements in Purdue Today, women's health clinics located in West Lafayette, Lafayette, and Indianapolis, and other social media platforms. Inclusion criteria are: all participants are undergoing natural perimenopause, English-speaking, and in general good health as documented by each woman's personal report that the participant is without any past history of a chronic health condition. The participants who have been using iron supplementation prior to the study may participate if the participants agree to discontinue the use of iron supplementation for the duration of the study. Lastly, individuals taking psychoactive drugs or with a history of hematological disorders will be excluded from the study.

(ii) Screening: Interested participants may either call or email the investigators using contact information found on the flyer or complete a short survey, which can be accessed via QR code on the flyer.

(iii) Randomization to treatment: Once the participants are classified as belonging to the IDA, ID, or IS groups, the participants will then be randomly assigned (within group) to receive either an iron supplement or a placebo for 4 months (previous studies have indicated a significant improvement in iron status and functional outcomes with a 4-month intervention period). FeoSol Original Iron Supplement Tablets (325 mg of ferrous sulfate containing 65 mg of elemental iron) will be used for the treatment (this have used this successfully in past studies) and 21st Century Gelatin Capsules (600 mg) will be used for the placebo (gelatin capsules have been used successfully for the placebo group, in past studies). Participants will be advised to take one capsule/tablet each day with food and store the given treatment out of the reach of children. Weekly phone calls or texts will be placed to each of the participants as a reminder to take supplements and to check tolerance to iron supplements. If intolerance to iron supplements are reported, participants may have an option to stop taking iron supplements. During weekly phone calls or texts, participants will also be asked if participants have started any new medications or become pregnant. If a participant becomes pregnant, participant's participation in the study will be terminated at that time. If a participant's physician is concerned about what the participants may be taking for this study, a participant's physician may contact either Mun Choi or Laura Murray-Kolb, whose contact information will be provided to all participants to share with physicians. Compliance will be measured through pill counts half-way through and at the end of the study. Group and treatment assignment will be blinded to the participants as well as the investigators.

(iv) Assessment of quality of life, mood, and family relationships: Assessment of these variables will take place before the blood draw at the Purdue Clinical Research Center at both baseline and endline of the study. Quality of life will be assessed using the self-administered MOS 36-Item Short Form Health Survey (SF-36) and the Menopause-Specific Quality of Life Questionnaire (MENQOL). These scales have been used extensively and shown to have good reliability with coefficients equal to or greater than 0.80 in most studies. For the assessment of mood, participants will be asked to complete the Beck Depression Inventory-II (BDI-II). The BDI-II is a 21-item self-reporting questionnaire and items will be summed to create a total score with higher scores indicating higher levels of depression. It has been widely used in research and clinical settings to measure depressive symptoms according to the diagnostic criteria listed in the Diagnostic and Statistical Manual for Mental Disorders. The BDI-II has been tested for validity and reliability in different populations and has good internal consistency and reliability. Family relationships will be assessed using the Family Adaptability and Cohesion Evaluation Scale IV Short Form (FACES-IV-SF). Ratio scores that are less than 1 indicate unbalanced families, or lower quality of interactions among family members. A recent validation study showed that the FACES-IV-SF demonstrated adequate reliability and good fit to the data as evidenced by the Cronbach's alphas for the subscales ranging from 0.63 (Enmeshment) to 0.93 (Satisfaction). All family members over the age of 12 (age of 13-17) that live with participants will be asked to complete this questionnaire. For family members who are under the age of 18, parental consent will be obtained when obtaining participant's written consent and youth assent will be obtained before the administration of the FACES-IV questionnaire via Qualtrics. For family members who are at or over the age of 18, individual consent will be obtained before the administration of the FACES-IV questionnaire via Qualtrics.

(v) Computerized measures of cognitive function: Executive function is an umbrella term that is used to describe complex mental operations such as planning, time perception, working memory, inhibition, self-monitoring and regulation, motor control, regulation of emotion, and motivation. To assess multiple domains of executive function in women with perimenopausal menorrhagia, the Psychology Experiment Building Language (PEBL) platform will be utilized to evaluate cognitive domains that were shown to be affected by iron status in previous studies. The PEBL is a software package allowing the creation of computerized tests for experimental use and neuropsychological testing, and has been widely used in different populations to assess cognitive performance. Thus, the following tests will be performed through the PEBL to assess five domains of cognition in perimenopausal women in a lighting and temperature-controlled testing environment:

Berg Card Sorting Test: The short 64-card version of the Berg Card Sorting Test (BCST) will be used as one measure of executive function in women. The test entails sorting cards based on shape, color, or number. A participant is given feedback (correct or incorrect) after each sorting, and participant may need to adjust sorting strategy based on the feedback received. During the test, the sorting rule changes (unbeknownst to the participant) and when it does, a participant must adjust sorting strategy accordingly. The BCST is used to distinguish diminished mental capacity and the shortened 64-card version of the BCST has been validated for use.

Attention Network Task: The Attention Network Task (ANT) is designed to assess three components of executive attention in a 30-minute testing session. The three components of executive attention that the ANT assesses include alerting (the ability to perceive that there is something to be attentive to), orienting (the ability to direct and shift attention to where it is needed), and conflict (the ability to filter out competing information). This test will present a sequence of visual stimuli where a participant will be shown cues in the form of either one or two asterisks in order to predict an upcoming target presentation and/or to orient the target's location. The cue is then followed by the presentation of target arrows, which may appear individually or in an arrangement of five arrows. A participant will be asked to respond by indicating which way the central arrow is facing, and scores for each network of attention will be calculated by reaction time subtractions of different stimulus combinations. The ANT has been performed by different populations and has been validated for use.

Go/No-Go Task: The Go/No-Go (GNG) Task is designed to assess one's ability to inhibit impulsivity while responding to go cues. During the GNG task, a participant is presented with a 2 x 2 pattern with one star in each square. The participant is instructed to follow a sequential presentation of letters and respond to the target letter (P) by pressing a button on the keyboard as quickly as possible, while suppressing responses to the non-target letter (R). The sequential presentation of letters is randomly generated and presented for 500 milliseconds in one of four squares with a 1500-millisecond interstimulus interval.

Tower of London Task: The Tower of London (TOL) Task is designed to assess one's efficiency in planning. During the TOL task, a participant is provided with colored disks that can be placed in three stacks with a maximum height of 1, 2, or 3 disks. Participants need to match a target configuration by moving one disk at a time and trying to do so in as few moves as possible. Prior to the task, practice trials are provided, and participants will be instructed to plan their entire sequence of moves mentally before initiating. The outcomes of this task include excess moves, planning time, and total time.

Sternberg Memory Search Task: The Sternberg Memory Search (SMS) Task is designed to evaluate one's working memory. During the SMS task, a participant is required to remember a series of letters presented one at a time and is then probed about whether particular letters were part of the presented set. In addition to accuracy, the amount of transmitted information, or throughput, will be calculated to correct for chance level \[throughput = {(uncorrected overall accuracy - 0.5) / 0.5} x the number of items included in the memory set\].

Eligibility criteria: Inclusion Criteria:

* Undergoing natural perimenopause
* English-speaking
* In general good health as documented by each woman's personal report that the participant is without any past history of a chronic health condition

Exclusion Criteria:

* Taking psychoactive drugs
* A history of hematological disorders

Primary outcomes:
measure: Iron Status Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Iron Status Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Iron Status Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Iron Status Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Iron Status Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Iron Status Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Iron Status Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Iron Status Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Inflammation Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Inflammation Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Cognitive Function Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Cognitive Function Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Cognitive Function Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Cognitive Function Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Cognitive Function Assessment
timeFrame: From enrollment to the end of treatment at 4 months
measure: Quality of Life
timeFrame: From enrollment to the end of treatment at 4 months
measure: Quality of Life
timeFrame: From enrollment to the end of treatment at 4 months
measure: Assessment of Mood
timeFrame: From enrollment to the end of treatment at 4 months
measure: Assessment of Family Relationships
timeFrame: From enrollment to the end of treatment at 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: West Lafayette
country: United States
facility: Stone Hall
state: Indiana
Study officials:
affiliation: Purdue University
name: Laura E Murray-Kolb, PhD
role: PRINCIPAL_INVESTIGATOR
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