Focusing on the Menopausal Transition to Improve Mid-Life Women's Health

NCT06975111 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 25-0943U1111-1322-1036
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

What if midlife women, who are inherently at an increased risk for future cardiometabolic disease due to transitioning into menopause, had access to a suite of evidence-based health interventions? Could these interventions reduce menopause-related inflammation, restore a healthier cardiometabolic profile, reverse epigenetic aging, and reduce bothersome menopausal symptoms? The ultimate goal of this work is to attenuate future disease and enhance women's quality of life, extend healthspan and increase productivity.

Conditions

Menopause; Menopause Hot Flashes; Menopause Related Conditions; Cardiovascular

Outcome Measures

Primary Outcomes (2)

• Epigenetic aging measurements of "PhenoAge"

  Change in epigenetic aging, as assessed by PhenoAge. PhenoAge calculates a biological age score based on key biomarkers circulating in the bloodstream. A lower PhenoAge score suggests slower biological aging, while a higher score indicates accelerated aging.

  Up to 2 years

• Epigenetic aging measurements of "GrimAge"

  Epigenetic aging, as assessed by GrimAge. GrimAge assesses lifespan from examining DNA Methylation.

  Up to 2 years

Secondary Outcomes (8)

• IL-1

  Up to 2 years

• TNF-alpha

  Up to 2 years

• IL-6

  Up to 2 years

• IL-8

  Up to 2 years

• Flow-mediated dilation

  Up to 2 years

Study Arms (5)

Preventative Health Advice

EXPERIMENTAL

Participants will be given preventative health advice and asked to wear an activity \& sleep monitor.

Behavioral: Life style intervention; Drug: Fezolinetant; Drug: Hormonal therapy

At Risk for Heart Disease

ACTIVE COMPARATOR

Medications will be given to each participant in this arm that lowers your heart disease risk.

Drug: Metformin; Drug: Anti-hypertensives; Drug: Lipid Lowering Medication; Behavioral: Life style intervention

Overweight Women

ACTIVE COMPARATOR

Women who fit in this category will receive medication for lowering insulin resistance and/or a weight loss medication.

Drug: Metformin; Drug: semaglutide

Women with Obesity

ACTIVE COMPARATOR

Women that are over a BMI of 30 kg/m2 will be offered a GLP-1 antagonist.

Drug: semaglutide

Women With Hot Flashes

ACTIVE COMPARATOR

Women with Hot flashes will have either hormonal or non-hormonal medication to reduce the number and/or severity of hot flashes.

Drug: Fezolinetant; Drug: Hormonal therapy

Interventions

Metformin DRUG

Metformin will be given to participants who have a elevated HbA1c and also for weightloss.

At Risk for Heart Disease; Overweight Women

semaglutide DRUG

Overweight women and women with obesity will take Semaglutide for weight-loss

Overweight Women; Women with Obesity

Anti-hypertensives DRUG

a. Antihypertensives, with the goal of maintaining blood pressure at 130/80 or lower per ACC guidelines19. Per current clinical guidelines and standard of care, hypertension will be treated first with monotherapy using either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), a calcium channel blocker, or a thiazide diuretic provided that are no contraindications.

Also known as: The use of angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), a calcium channel blocker, or a thiazide diuretic.

At Risk for Heart Disease

Lipid Lowering Medication DRUG

. First line agents will be generic statin medications (atorvastatin or rosuvastatin)whichever is covered by the participant's health insurance), barring contraindication to their use.

Also known as: The use of generic statins

At Risk for Heart Disease

Life style intervention BEHAVIORAL

will simply be followed and given preventive advice (maintenance of a normal BMI and physical activity, moderation in salt intake, and no more than 1 alcoholic drink per day). They will be provided with a wearable activity monitor. This advice will be based on guidelines by the American Heart Association and the Menopause Society.

At Risk for Heart Disease; Preventative Health Advice

Fezolinetant DRUG

Women with menopausal symptoms will be treated with hormone therapy (estrogen and progesterone) if appropriate, or with a neurokinin receptor antagonist (Fezolinetant). This can be treatment for women in any arm of the study as well as an arm by its self.

Preventative Health Advice; Women With Hot Flashes

Hormonal therapy DRUG

Participants will be treated with estrogen and/or progesterone for treatment of hot flashes in women during the study.

Preventative Health Advice; Women With Hot Flashes

Eligibility Criteria

• Age: 45 Years - 55 Years
• Gender Eligibility Details: We are studying the menopausal transition which only happens in women.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• aged 45-55
• In the late menopausal transition, defined as 60 days of amenorrhea but less than 365 days of amenorrhea18
• No current use of hormone therapy or hormonal contraception
• Presence of a uterus and at least one ovary in order to track menstrual patterns
• Have a smartphone and broadband access adequate to accept telehealth appointments

You may not qualify if:

• Lack of broadband access (activity and survey data will be collected electronically whenever possible and some visits will be via telehealth)
• Lack of regular menstrual periods in mid-reproductive life (ages 25-38) when not on hormones or not pregnant.
• Pregnancy or actively trying to get pregnant
• Inability to adhere to study protocol schedule
• Untreated alcoholism
• Un- Diagnosed abnormal uterine bleeding
• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN 2) for participants with a BMI\> 30 kg/m2.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado-School of Medicine

Aurora, Colorado, 80045, United States

RECRUITING

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MeSH Terms

Interventions

Metformin; semaglutide; Antihypertensive Agents; Angiotensin Receptor Antagonists; fezolinetant

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Molecular Mechanisms of Pharmacological Action

Study Officials

• Nanette Santoro, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carrie Hsu, BA

CONTACT

303-724-5276; carrie.hsu@cuanschutz.edu

Nalia Naushad

CONTACT

naila.naushad@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be placed into treatment interventions based on their health and screening tests.

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 16, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (1)