---
project: Open Peptide Project
document: Registry Protocol
version: 1.1 (DRAFT, revised by Dr. Nova Reyes, Oct 14 2026)
status: Public Release v1.1 (Ethics Route Option B: Independent IRB Determination Prior to Enrollment)
changes_from_1.0: see Appendix A
---

# The Open Peptide Project Registry (OPPR)
*A prospective, decentralized, self-reported observational registry of research peptide use*

## 1. Plain-language summary
Most research peptides have never been studied properly in humans. This registry collects structured, prospective data from people who have already decided to use them: before they start, while they use them, and after. It is not a trial. The project assigns, supplies, sells, and recommends nothing. You use what you were going to use, and we measure what happens in a way that can be analyzed.

## 2. Design
Prospective, decentralized, longitudinal, self-reported, single-cohort observational registry with a within-person interrupted time-series structure.

Participants enroll before they start and complete a 14-day pre-baseline with **three outcome measurements (day −14, −7, 0)**. This estimates each person's pre-initiation trajectory (for example, natural healing), so the primary analysis compares the rate of change before versus after initiation rather than a single before/after difference.

## 3. Objectives
**Primary:** estimate the change in slope of indication-specific function (PSFS) after initiation of a research peptide, relative to each participant's pre-initiation slope, through week 12.

**Secondary:**
- Characterize real-world dosing (calculated mcg), route, frequency, duration, and stacking
- Estimate incidence and type of adverse events, compared per week before versus after initiation
- Compare outcomes across batch tiers (verified, declared, unverified), exploratory and adjusted
- Responder proportion (PSFS improvement ≥ 2 points, minimum clinically important difference; value to be confirmed against literature before registration)
- Objective function measures (Section 7)

**Exploratory:** dose-response, sex and age subgroups, adherence-stratified outcomes, single- vs multi-compound use.

## 4. Eligibility
**Inclusion:**
- Age 18+
- Already intending to initiate a research peptide within 30 days of enrollment (the project does not encourage initiation)
- Musculoskeletal or tendon complaint (launch module)
- Willing to complete the 14-day pre-baseline and 12 weeks of follow-up
- Phone with camera and internet

**Exclusion:**
- Currently using the target compound (≥ 4-week washout required)
- Concurrent participation in another interventional study
- Pregnant or breastfeeding, or planning pregnancy during follow-up
- Any condition making self-report unreliable, at the participant's own judgement

**Recorded, not excluded:** concurrent medication, supplements, training, and **every concurrent peptide** (recorded as an exposure). Injury duration is recorded; **chronic (≥ 3 months)** is the pre-specified primary analysis population, acute cases analyzed separately.

## 5. Recruitment and consent
Recruitment via the project site, newsletter, peptide communities, and word of mouth, addressed only to people who have already decided to use a peptide. No outcome claims, testimonials, or interim results in recruitment material. No links to vendors.

Electronic informed consent covering:
- What is collected and why; that the study is observational and the project assigns, supplies, and recommends nothing
- Voluntary participation; withdrawal at any time, with collected data retained unless the participant opts out
- Pseudonymous participant IDs; contact details (email/phone for reminders and safety follow-up) stored separately from study data and never published
- Photos stripped of location and device metadata and stored separately from survey answers
- Publication of aggregate and de-identified participant-level data, with small cells (rare compound/age/sex/injury combinations) grouped or suppressed
- The registry does not provide medical care; seek care first for any concerning symptom
- Conflicts of interest and funding (Section 15)
- Contact point for questions and adverse events

Consent text published in full on the project site.

## 6. Schedule of assessments
| Timepoint | Exposure log | Adverse events | Outcomes | Batch capture |
|---|---|---|---|---|
| Day −14, −7, 0 | Concurrent compounds | Weekly symptom checklist | Core + module instruments | Product photo |
| Day 0 (initiation) | Daily | Daily prompt | — | Vial + batch photo, reconstitution details |
| Weeks 1–12 | Daily | Daily prompt + weekly checklist | Weekly | At batch change |
| Weeks 13–52 | Weekly | Weekly checklist | Monthly | At batch change |

Daily log target: about 20 seconds. Weekly target: under 5 minutes.

## 7. Instruments
Free-licensed instruments only.

**Core (all):** demographics, training status, concurrent meds/supplements/peptides; PROMIS Global Health-10; PROMIS Sleep Disturbance 4a; Global Rating of Change (weekly).

**Musculoskeletal launch module:**
- **PSFS (primary):** three participant-nominated activities, 0–10
- Numeric Pain Rating Scale 0–10
- Condition-specific where applicable: VISA-A, VISA-P, QuickDASH, KOOS (licensing of each to be confirmed before registration)
- **Objective secondary measures (phone-based):** 30-second sit-to-stand, timed short walk using phone motion sensors, guided range-of-motion photo using an on-screen outline and level check; weekly step count (self-entered); grip strength by hand dynamometer (optional)

**Other modules** (gastrointestinal, sleep/energy) are descriptive only until separately powered and are not part of launch.

**Adverse-event checklist (weekly, from baseline):** injection-site reaction, nausea, headache, flushing, dizziness, heart rate/palpitations, sleep change, appetite change, mood change, other (free text).

## 8. Exposure and batch capture
- **Daily:** compound(s), dose in syringe units, route, time, missed doses. Calculated mcg = (units ÷ syringe units per mL) × (vial mg × 1000 ÷ diluent mL); for a U-100 syringe, units per mL = 100 (e.g., 5 mg in 2 mL drawn to 10 units = 250 mcg). Non-U-100 syringes flagged; out-of-range values prompt a re-check; participant confirms the calculated value.
- **At each batch change:** photo of vial label and batch number; vial strength (mg), bacteriostatic water volume (mL), syringe type.
- **Blends** are decomposed into component compounds; each component is recorded as an exposure.

**Batch tiers:**
1. **Verified:** batch tested under the Open Peptide Standard (below), result published
2. **Declared:** batch number captured, not tested
3. **Unverified:** no batch captured

**Open Peptide Standard (testing, updated Oct 25, 2026):** test vials purchased anonymously at retail by the project or participants (at least 2 blind vials per batch: one for analytical chemistry and one sealed for microbiological testing, plus a third retained vial where feasible; never vendor-supplied; vendor certificates do not count); sent to an ISO/IEC 17025-accredited lab with peptide HPLC/LC-MS scope under a project code only; lab report verified against the lab's own verification system and published within 7 days of arrival, pass or fail.
- **Three-tier test panel:**
  - **Core tier (every tested batch):** Identity by LC-MS / HRMS (measured mass within ±0.5 Da or ±10 ppm of theoretical mass, plus RP-HPLC retention-time match where a reference standard exists), purity by RP-HPLC (214–220 nm with full chromatogram and individual impurity reporting), and vial content / quantity by HPLC assay against a reference standard (±10% of label [90.0–110.0%] passing, with lab measurement uncertainty reported).
  - **Injectable tier (vials sold for reconstitution / injection):** Core tier plus bacterial endotoxins (USP `<85>` kinetic LAL reported in EU/vial against a published per-vial cutoff; no per-dose calculation is used) and sterility / bioburden (USP `<71>` or labeled TAMC/TYMC bioburden, with the statistical caveat that single-vial testing cannot guarantee lot-wide sterility).
  - **Full characterization tier (extended & risk-based spot checks):** Injectable tier plus net peptide content (amino acid analysis or CHN nitrogen mass balance), Karl Fischer water content, TFA / acetate counter-ion content (USP `<503>` / `<503.1>`), and risk-based elemental impurities (USP `<232>`/`<233>` ICP-MS) and residual solvents (USP `<467>` headspace GC).
- **Tiered HPLC purity & vial content grading scale:**
  - **`A+` (≥ 98.0% HPLC purity, 90.0–110.0% labeled content):** Exceeds standard; receives an additional **"Pharma-comparable"** impurity flag when no single unidentified impurity exceeds 0.5% (referencing the FDA 2021 synthetic peptide ANDA guidance threshold as an analytical benchmark only, never claiming "pharmaceutical grade" or "safe"; if individual impurities are not reported, the flag reads "Not assessed").
  - **`Pass` (96.0–97.9% HPLC purity, 90.0–110.0% labeled content):** Meets standard (identity and endotoxin pass); any single unidentified impurity > 1.0% is flagged on the batch report.
  - **`Caution` (92.0–95.9% HPLC purity, or vial content 80.0–89.9% / 110.1–120.0%):** Below passing purity or content tolerance; published with a Caution badge on the batch report.
  - **`Fail` (< 92.0% HPLC purity, vial content < 80.0% or > 120.0%, failed LC-MS identity, or failed endotoxin/sterility):** Fails standard. Failed LC-MS identity or failed endotoxin/sterility is an automatic overall **Fail** regardless of HPLC purity.
- **Batch-only scope (vendor strike system removed Oct 25, 2026):** Every result is published with its batch number, exact HPLC purity %, and test date directly inside the badge. Grades attach strictly to the tested batch number and test date, expire after a stated period, and never certify, endorse, grade, or penalize a vendor or brand. Batches from any related party (including Peptide Hall, owned by the project lead's brother) are labeled as related-party results and must be confirmed by a second unaffiliated lab; related parties may not advertise.
- **Contracted Anchor Lab & Referee Lab (Preferred Volume Pricing, Zero Referral Kickbacks):** To maximize the number of blind batches tested per dollar contributed, the Open Peptide Project may contract with one or more primary ISO/IEC 17025-accredited laboratories ("Anchor Labs", whose accreditation scope explicitly covers quantitative RP-HPLC, LC-MS identity, and USP `<85>` kinetic LAL endotoxin) for preferred nonprofit or volume per-sample pricing, while routing at least **10% of batches (plus all disputed `Fail` re-tests and all related-party batches)** to a second, unaffiliated ISO/IEC 17025 referee laboratory. Preferred pricing applies strictly to invoices paid by the Open Peptide Project for blind testing—the project never accepts referral commissions, kickbacks, or revenue-sharing when vendors or third parties submit samples to a partner lab.

## 9. Sample size
Within-person analysis detecting a standardized effect of d = 0.3, 80% power, two-sided α = 0.05: **≈ 90 completers** (to be confirmed by simulation under the slope model before registration). With 35% attrition, target **150 enrolled in the musculoskeletal module** (stretch 500). Re-estimated after the first 50 completers; amendment logged.

## 10. Data management
- Pseudonymous IDs; contact details stored separately
- Documented, exportable platform; automated range/logic checks
- Weekly completeness report; nudge after 2 consecutive missed weeks; lost to follow-up at 4
- Data dictionary and form versions frozen before enrollment; any change logged as an amendment
- De-identified CSV and analysis code published at completion, with small-cell suppression

## 11. Statistical analysis plan
**Primary analysis:** piecewise (segmented) linear mixed model of PSFS over time, with random intercept and random slope per participant; fixed effects for time, a post-initiation indicator (level change), and time since initiation (slope change). The primary estimand is the **slope change** after initiation. Primary population: chronic-injury participants with ≥ 2 baseline and ≥ 1 post-initiation measurement.

**Secondary:** same model for secondary instruments; responder proportion (≥ 2-point PSFS improvement at week 12); adverse events as rate per participant-week, before versus after initiation, with exact confidence intervals.

**Pre-specified subgroups (exploratory, unadjusted):** batch tier; single- vs multi-compound; age < 40 vs ≥ 40; sex; training status; acute vs chronic.

**Multiplicity:** one primary endpoint; all others reported with confidence intervals and labeled unadjusted.

**Missing data:** primary under missing-at-random; sensitivity with multiple imputation and a pattern-mixture (worse-outcome-for-dropouts) analysis; attrition reported by reason.

**Statistics executed in published code only,** never by hand or by language-model reasoning.

## 12. Pre-specified limitations
- Self-selection
- Unblinded self-report; expectation effects not controlled
- Regression to the mean and natural healing, partly addressed by the baseline slope, not eliminated
- Non-random attrition
- Concurrent changes in training, diet, sleep, and other compounds
- Heterogeneous doses, products, and routes
- Not generalizable to the general population
- Batch-tier comparisons are non-randomized

**No claim of causality.** The registry produces associations and within-person change estimates.

## 13. Safety
- Daily "anything unusual?" prompt plus weekly structured checklist (from baseline); free text anytime
- **Serious event** (any of): death, life-threatening event, emergency department visit or hospitalization, persistent disability, discontinuation due to the event, or participant-rated severe
- Serious events reviewed by a named project safety reviewer within 48 hours; participant advised to seek care; event logged and published
- Causality: unlikely / possible / probable, participant report with project adjudication
- Pregnancy during follow-up: participant asked to report; follow-up to outcome if they consent
- All events published, including those judged unrelated
- The registry does not provide medical care

## 14. Ethics
Observational and decentralized. **[DECISION PENDING — ADAM]:**
- Option A: self-review with published protocol, stated plainly in registration and on the site
- Option B (recommended): as A, plus a concurrent request to an independent commercial IRB for an exemption determination before or shortly after enrollment opens

Described only as a "decentralized, patient-led observational registry," never a "clinical trial." Any future study that changes what participants do (e.g., self-blinding) requires IRB review before it begins. Any study in which the project supplies a compound requires FDA regulatory counsel and an IND or other lawful pathway; none is planned under this protocol.

## 15. Transparency and conflicts of interest
- Protocol versioned and timestamped before enrollment; registered on OSF with a DOI
- Every amendment logged with date and reason
- Negative and null results published
- **Conflicts and funding disclosed on every output: [PENDING — LLC ownership; any ties of team members to peptide sales, including Peptide Hall]**
- **Funding safeguards (if any vendor revenue is accepted):** batches selected for testing by a published rule (most-used in registry plus random selection), never by vendor request or payment; results published automatically within 7 days of lab report receipt with a public dated log; one retest rule for all; no advertising on test-result, library, or registry pages; test results attach strictly to individual batches (never certifying, grading, or penalizing vendors, with the vendor strike and sponsor-suspension ladder removed Oct 25, 2026); any future sponsor or advertising policy is separate from batch testing and subject to independent legal counsel review; advertisers get no preview, no pre-publication response, and cannot remove results; revenue by source published quarterly
- No affiliate revenue tied to peptide purchases
- **Board-member, Anchor Lab, and funder conflict-of-interest (COI) firewall:** Every board member and officer must file a written annual conflict-of-interest disclosure published on `/disclosure/`; any individual with direct or indirect financial ties to a peptide vendor, compounding pharmacy, or telehealth peptide seller is excluded from sitting on the board or voting on batch selection, laboratory selection, grading thresholds, or Evidence Library content. Anchor Lab and Referee Lab contracts are restricted strictly to fee-for-service blind testing invoices paid by the project (with zero referral fees, kickbacks, or revenue-sharing from third-party/vendor testing), and funders/sponsors have zero input into which batches are tested, which lab runs a batch, or when and how results are published.

## 16. Pre-registration text (update after decisions; paste only after approval)
**Title:** The Open Peptide Project Registry: a prospective decentralized observational registry of research peptide use.
**Registration date:** [DATE], prior to enrollment.
**Design:** Prospective, single-cohort, decentralized, self-reported observational registry with a 14-day, three-measurement pre-baseline per participant (interrupted time series within person).
**Primary objective/endpoint:** change in slope of Patient-Specific Functional Scale (0–10, three nominated activities) after initiation relative to pre-initiation slope, through week 12, in chronic musculoskeletal participants.
**Eligibility:** adults 18+, already intending to initiate a research peptide within 30 days, not currently using it, not pregnant, musculoskeletal complaint, willing to complete baseline and 12 weeks of follow-up.
**Target sample:** 150 enrolled, ≈ 90 completers, musculoskeletal module.
**Analysis:** piecewise linear mixed model, random intercept and slope; primary estimand slope change. Secondary: responder analysis, adverse event rates before vs after. Pre-specified exploratory subgroups: batch tier, single vs multi-compound, age, sex, training status, acute vs chronic. One primary endpoint.
**Ethics:** [Option A or B].
**Conflicts/funding:** [per Section 15].
**Pre-specified limitations:** as Section 12.
**Data:** de-identified participant-level CSV (small cells suppressed) and analysis code published on completion.

---
## Appendix A: Changes from v1.0
1. Three baseline measurements; primary analysis changed to slope change (segmented mixed model), resolving the double-counted baseline.
2. Primary population: chronic injuries (≥ 3 months); acute analyzed separately.
3. Sample size stated as musculoskeletal-module only; other modules descriptive.
4. Every concurrent peptide recorded as an exposure; blends decomposed.
5. Dose captured as syringe units plus reconstitution, converted to mcg.
6. Batch tier comparison labeled exploratory/non-randomized.
7. Weekly adverse-event checklist from baseline; serious-event definition expanded; 48-hour review; pregnancy handling; resolves daily/weekly inconsistency.
8. Pregnancy added to exclusions.
9. Objective phone-based secondary measures added.
10. Responder analysis added.
11. Contact details separated; photo metadata stripped; small-cell suppression.
12. Open Peptide Standard defined (anonymous purchase, accredited blind lab, full panel, batch-level expiring results, related-party labeling).
13. Ethics section rewritten with Option A/B decision; no self-declared exemption.
14. Funding safeguards; affiliate revenue removed.
15. Pre-registration text updated to match.
16. Dose formula corrected for syringe units per mL.
17. Three-tier Open Peptide Standard panel (`Core`, `Injectable`, `Full`), 4-tier HPLC purity scale (`A+` ≥98.0% with Pharma-comparable impurity flag at ≤0.5% single impurity, `Pass` 96.0–97.9%, `Caution` 92.0–95.9%, `Fail` <92.0%), batch-only grading with vendor strike / sponsor-suspension system removed (Oct 25, 2026); mandatory second-lab check and no advertising for related parties.
18. Contracted ISO/IEC 17025 Anchor Lab & 10% Unaffiliated Referee Lab model (preferred nonprofit/volume per-sample pricing on project invoices only; zero referral commissions or kickbacks) and written annual board/funder COI firewall added to Sections 8 and 15 (Oct 25, 2026).

## Appendix B: Items to confirm before registration
- PSFS minimum clinically important difference
- Licensing of VISA-A, VISA-P, QuickDASH, KOOS
- Sample size by simulation under the slope model
- Endotoxin and heavy-metal limits and final pass thresholds
- Named safety reviewer
- Adam's decisions: ethics route, LLC ownership/conflicts, vendor revenue