## Protocol Section
### Identification Module
**NCT ID:** NCT06424834

**Acronym:** MVP-ANOCA

**Brief Title:** Efficacy of Targeted Medical Therapy in Angina and Nonobstructive Coronary Arteries

**Official Title:** A Randomized Controlled Study of Targeted Medical Therapy Versus Placebo for Angina and Non- Obstructive Coronary Arteries: The MVP-ANOCA Study

#### Organization Study ID Info
**ID:** IRB-75085
#### Organization
**Class:** OTHER
**Full Name:** Stanford University
#### Secondary ID Infos
**Domain:** American Heart Association
**ID:** 24POST1189688
**Type:** OTHER_GRANT
### Status Module
#### Completion Date
**Date:** 2026-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-12
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** American Heart Association

#### Lead Sponsor

**Class:** OTHER

**Name:** Stanford University

#### Responsible Party

**Investigator Affiliation:** Stanford University

**Investigator Full Name:** Christopher Chi-Yuen Wong

**Investigator Title:** Postdoc

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The goal of this clinical trial is to learn if targeted medical therapy will improve symptoms and quality of life in patients with angina and non-obstructive coronary arteries compared to placebo, after the underlying cause of the chest pain has been ascertained by coronary function testing.

Participants will be treated with either medications that target the underlying cause of their chest pain or placebo for 50 days. They will be asked to complete a series of questionnaires to evaluate their quality of life at the beginning and end of the study.

### Conditions Module

**Conditions:**

- Angina Pectoris

- Microvascular Angina

- Vasospastic Angina

- Myocardial Bridge of Coronary Artery

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 150

**Type:** ESTIMATED

**Phases:**

- PHASE2

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 1. Epicardial or microvascular coronary spasm: Amlodipine 2.5mg initial dose, 10mg max dose
2. Coronary microvascular dysfunction: Nebivolol 5mg initial dose, 20mg max dose
3. Myocardial Bridge: Nebivolol 5mg initial dose, 20mg max dose
4. Mixed epicardial/microvascular spasm and coronary microvascular dysfunction/myocardial bridge: Amlodipine 2.5mg initial dose, 10mg max dose; PLUS Nebivolol 5mg initial dose, 20mg max dose

Participants will take their assigned therapy after randomization. Weekly person via in-person visit or telephone is performed to uptitrate therapy to the maximally tolerated dose. After 3 weeks, the initial drug titration phase is completed and a final dose reached. Participants are then instructed to take the maximally tolerated dose for 4 weeks to the conclusion of the study.

**Intervention Names:**

- Drug: Amlodipine

- Drug: Nebivolol

**Label:** Targeted medical therapy

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 1. Epicardial or microvascular coronary spasm: Placebo
2. Coronary microvascular dysfunction: Placebo
3. Myocardial Bridge: Placebo
4. Mixed epicardial/microvascular spasm and coronary microvascular dysfunction/myocardial bridge: Placebo

Participants will take their assigned therapy after randomization. Weekly person via in-person visit or telephone is performed to uptitrate therapy to the maximally tolerated dose. After 3 weeks, the initial drug titration phase is completed and a final dose reached. Participants are then instructed to take the maximally tolerated dose for 4 weeks to the conclusion of the study.

**Intervention Names:**

- Drug: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Targeted medical therapy

**Description:** Amlodipine taken once orally daily at a starting dose of 2.5mg, uptitrated to a maximum of 10mg if tolerated.

**Name:** Amlodipine

**Other Names:**

- Norvasc

- Katerzia

- Norliqva

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Targeted medical therapy

**Description:** Nebivolol taken once orally daily at a starting dose of 5mg, uptitrated to a maximum of 20mg if tolerated.

**Name:** Nebivolol

**Other Names:**

- Bystolic

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Placebo

**Description:** Placebo taken once orally daily.

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Change in Seattle Angina Questionnaire summary score at 7 weeks compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.

**Measure:** Seattle Angina Questionnaire summary score

**Time Frame:** 7 weeks

#### Secondary Outcomes

**Description:** Change in EuroQol 5 dimension score - 5L index score at 7 weeks compared to baseline. The index ranges from -0.573 to 1.000, with a higher score indicating a better outcome.

**Measure:** EuroQol 5 dimension - 5L index score

**Time Frame:** 7 weeks

**Description:** Change in EuroQol 5 dimension score - 5L visual analogue score at 7 weeks compared to baseline. The index ranges from 0 - 100, with a higher score indicating a better outcome.

**Measure:** EuroQol 5 dimension - 5L visual analogue score

**Time Frame:** 7 weeks

**Description:** Change in PHQ-4 at 7 weeks compared to baseline. The score ranges from 0 - 12, with a higher score indicating a worse outcome.

**Measure:** PHQ-4 score

**Time Frame:** 7 weeks

**Description:** Change in Treatment Satisfaction Questionnaire for Medication score at 7 weeks compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.

**Measure:** Treatment Satisfaction Questionnaire for Medication score

**Time Frame:** 7 weeks

**Description:** Change in Seattle Angina Questionnaire summary score at 7 weeks stratified by specific chest pain endotypes at 7 weeks compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.

**Measure:** Seattle Angina Questionnaire summary score stratified by specific chest pain endotypes

**Time Frame:** 7 weeks

**Description:** EuroQol 5 dimension - 5L index score at 7 weeks stratified by specific chest pain endotypes at 7 weeks compared to baseline. The index ranges from -0.573 to 1.000, with a higher score indicating a better outcome.

**Measure:** EuroQol 5 dimension - 5L index score stratified by specific chest pain endotypes

**Time Frame:** 7 weeks

**Description:** EuroQol 5 dimensions - 5L visual analogue score at 7 weeks stratified by specific chest pain endotypes at 7 weeks compared to baseline. The index ranges from 0 - 100, with a higher score indicating a better outcome.

**Measure:** EuroQol 5 dimensions - 5L visual analogue score stratified by specific chest pain endotypes

**Time Frame:** 7 weeks

**Description:** PHQ-4 score at 7 weeks stratified by specific chest pain endotypes at 7 weeks compared to baseline. The score ranges from 0 - 12, with a higher score indicating a worse outcome.

**Measure:** PHQ-4 scores stratified by specific chest pain endotypes

**Time Frame:** 7 weeks

**Description:** Treatment Satisfaction Questionnaire for Medication scores at 7 weeks stratified by specific chest pain endotypes at 7 weeks compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.

**Measure:** Treatment Satisfaction Questionnaire for Medication score stratified by specific chest pain endotypes

**Time Frame:** 7 weeks

**Description:** Change in Seattle Angina Questionnaire summary score stratified by baseline angina frequency at at 7 weeks compared to baseline. The score ranges from 0 - 100, with a higher score indicating a better outcome.

**Measure:** Seattle Angina Questionnaire summary score stratified by baseline angina frequency

**Time Frame:** 7 weeks

**Description:** Difference between targeted medical therapy group and placebo group in proportion of patients with good response (Seattle Angina Questionnaire summary score ≥ 10), no angina (Seattle Angina Questionnaire angina frequency score = 100), and excellent health status (Seattle Angina Questionnaire summary score ≥ 75).

**Measure:** Proportion of patients with good response, no angina, and excellent health status

**Time Frame:** 7 weeks

**Description:** Incidence of bleeding, coronary dissection, stroke, periprocedural myocardial infarction, non-self-limiting arrhythmias during the index coronary function testing procedure

**Measure:** Safety endpoints

**Time Frame:** Baseline

**Description:** Difference between targeted medical therapy group and placebo group in incidence of cardiac death, myocardial infarction, and hospital presentation for unstable angina.

**Measure:** Major adverse cardiac events

**Time Frame:** 7 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* All patients with stable angina referred to the Stanford University Hospital cardiac catheterization laboratory for clinically indicated coronary function testing are eligible for inclusion into the study.

Specific inclusion criteria for randomization:

* Absence of significant epicardial coronary artery disease on angiography
* Fractional flow reserve \> 0.80

And ≥ 1 of the following:

* Epicardial coronary spasm on acetylcholine testing
* Microvascular spasm on acetylcholine testing
* Coronary flow reserve \< 2.0
* Index of microcirculatory resistance ≥ 25
* Myocardial bridge on intravascular ultrasound with dobutamine resting full-cycle ratio ≤ 0.76

Exclusion Criteria:

* Acute coronary syndrome less than one week prior to enrolment
* Cardiomyopathy
* Contraindications to beta-blockers or calcium channel blockers
* Baseline systolic blood pressure \< 95 mmHg
* Baseline heart rate \< 55 bpm

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ccywong@stanford.edu

**Name:** Christopher Wong, MBBS, PhD

**Phone:** (650) 725 5909

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Palo Alto

**Contacts:**

***Contact 1:***

- **Email:** ccywong@stanford.edu

- **Name:** Christopher Wong, MBBS, PhD

- **Phone:** 650-725-5909

- **Role:** CONTACT

***Contact 2:***

- **Name:** Jennifer Tremmel, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Stanford Hospital

**State:** California

**Zip:** 94304

#### Overall Officials

**Official 1:**

**Affiliation:** Stanford University

**Name:** Jennifer Tremmel, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000017202

- Term: Myocardial Ischemia

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002637

- Term: Chest Pain

- ID: D000010146

- Term: Pain

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000000789

- Term: Angina, Unstable

- ID: D000003330

- Term: Coronary Vessel Anomalies

- ID: D000006330

- Term: Heart Defects, Congenital

- ID: D000018376

- Term: Cardiovascular Abnormalities

- ID: D000000013

- Term: Congenital Abnormalities

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M4117

- Name: Angina Pectoris

- Relevance: HIGH

- As Found: Angina

- ID: M19816

- Name: Microvascular Angina

- Relevance: HIGH

- As Found: Microvascular Angina

- ID: M4118

- Name: Angina Pectoris, Variant

- Relevance: HIGH

- As Found: Vasospastic Angina

- ID: M27563

- Name: Myocardial Bridging

- Relevance: HIGH

- As Found: Myocardial Bridge

- ID: M6546

- Name: Coronary Artery Disease

- Relevance: LOW

- As Found: Unknown

- ID: M19506

- Name: Myocardial Ischemia

- Relevance: LOW

- As Found: Unknown

- ID: M10543

- Name: Ischemia

- Relevance: LOW

- As Found: Unknown

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13066

- Name: Pain

- Relevance: LOW

- As Found: Unknown

- ID: M5882

- Name: Chest Pain

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M4119

- Name: Angina, Unstable

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M6552

- Name: Coronary Vessel Anomalies

- Relevance: LOW

- As Found: Unknown

- ID: M9418

- Name: Heart Defects, Congenital

- Relevance: LOW

- As Found: Unknown

- ID: M20503

- Name: Cardiovascular Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: T4716

- Name: Prinzmetal's Variant Angina

- Relevance: HIGH

- As Found: Vasospastic Angina

### Condition Browse Module - Meshes

- ID: D000000787

- Term: Angina Pectoris

- ID: D000017566

- Term: Microvascular Angina

- ID: D000000788

- Term: Angina Pectoris, Variant

- ID: D000054084

- Term: Myocardial Bridging

### Intervention Browse Module - Ancestors

- ID: D000000959

- Term: Antihypertensive Agents

- ID: D000002121

- Term: Calcium Channel Blockers

- ID: D000049990

- Term: Membrane Transport Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000077264

- Term: Calcium-Regulating Hormones and Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000014665

- Term: Vasodilator Agents

- ID: D000058665

- Term: Adrenergic beta-1 Receptor Agonists

- ID: D000000318

- Term: Adrenergic beta-Agonists

- ID: D000000322

- Term: Adrenergic Agonists

- ID: D000018663

- Term: Adrenergic Agents

- ID: D000018377

- Term: Neurotransmitter Agents

### Intervention Browse Module - Browse Branches

- Abbrev: AnAg

- Name: Antihypertensive Agents

- Abbrev: ChanBlk

- Name: Channel Blockers

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

### Intervention Browse Module - Browse Leaves

- ID: M19600

- Name: Amlodipine

- Relevance: HIGH

- As Found: Diabetic

- ID: M276

- Name: Nebivolol

- Relevance: HIGH

- As Found: ICSI

- ID: M4277

- Name: Antihypertensive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M5381

- Name: Calcium

- Relevance: LOW

- As Found: Unknown

- ID: M5384

- Name: Calcium Channel Blockers

- Relevance: LOW

- As Found: Unknown

- ID: M5398

- Name: Calcium, Dietary

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M17412

- Name: Vasodilator Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20746

- Name: Adrenergic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M3670

- Name: Adrenergic beta-Agonists

- Relevance: LOW

- As Found: Unknown

- ID: M3673

- Name: Adrenergic Agonists

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000017311

- Term: Amlodipine

- ID: D000068577

- Term: Nebivolol

### Misc Info Module

- Version Holder: 2024-05-31
